"Doof 101" is the two hundred twenty-first episode of Phineas and Ferb, and notably the last standard-length (11 minutes) episode to air.
Dr. Doofenshmirtz is sentenced to community service for being evil, and much to his daughter Vanessa's chagrin, he is assigned to teach science at her high school. Meanwhile, a trio of bugs embark on a journey to become the first insects to communicate with humans.
School has started at Danville High, and Vanessa heads to her classroom, where she explains to her friends Lacey and Becky about her father's last scheme which involves erasing blue colors from paintings at a museum. Around the same time, Johnny arrives, moping over his failed relationship with Vanessa, despite Vanessa telling him they haven't gone out that long, only for Johnny to retort that it hasn't been the same ever since.
When class is about to begin, Principal Lang arrives, announcing that there's been a change in school faculty, presenting out the class's new science teacher, who is none other than Heinz Doofenshmirtz himself, much to Vanessa's shock. It turns out that the reason behind this was because of his last scheme that almost put him into trouble with the authorities, so he chose to do community service in Danville High rather than doing his sentence in jail. As Doofenshmirtz assures to Principal Lang that he'll be doing fine with the students, the principal states that he'll be watching him before leaving the classroom.
Doofenshmirtz is about the spell his name to the class, only to be interrupted by a nervous Vanessa, who drags him outside of the classroom to talk to him, fearing that he might further embarrass her again. Johnny joins them as he continues moping, resulting Doofenshmirtz to call him a crybaby. Becky then arrives, asking if Doofenshmirtz is ever gonna give Vanessa 'special treatment' just because she is his daughter, only for Vanessa to retort that he won't. Doofenshmirtz then tells the kids to get back to the classroom at once.
In Principal Lang's office, his secretary Mrs. Pierpoint notices that Lang is brooding and asks why is he doing so. It was then Lang confesses that he doesn't approve of having Doofenshmirtz to work in his school, stating that he was once a college rival of his during the 80s. Lang also admits to being very jealous of Doofenshmirtz for winning the heart of Charlene, the only woman he ever fell in love with. Mrs. Pierpoint points out that the two are divorced and suggests to Lang to give up his grudge against Doofenshmirtz, but he refuses, stating that there will be no use for his uni-brow if otherwise.
Back in the classroom, Doofenshmirtz decides to bring the topic of genetics as a lecture to the class. Using a hair follicle from Johnny's scalp, Doofenshmirtz places it inside a Petri dish and uses a microscope to explain to the students that everything defined in Johnny is all explained through the strands of DNA inside his hair sample. Doofenshmirtz also states that the genetic code itself is fragile since a few base pairs can be moved, and that the DNA of a human can be a few bases away from that of a primate's or a reptile's, since humans were evolved from both creatures millions of years ago. As Doofenshmirtz continues his lecture to the class while moving a few base pairs inside the hair sample for a demonstration, three talking bugs (Napoleon, Wendell, and Floyd) watch him from below Doofenshmirtz's table. Napoleon suggests that he and his friends take on the challenge on being the first insects to communicate with humans, and to do so, they decide to climb up to the top of the table. Wendell volunteers to use a hook (made out of a paper clip) to climb themselves up, but he accidentally grabs a beaker instead, causing it to fall into the floor and trap the bugs.
As the beaker falll, it causes several books on the table to fall onto a scale balance, sending needles with wires into the air. The needles then land onto a potato clock and a dead frog, causing the frog to move his legs and kick the dish into Johnny's face. After recovering the dish from Johnny's face, Doofenshmirtz hopes that the mutated DNA inside the hair sample doesn't mix up with Johnny's. However, that wasn't the case when Johnny grew a reptilian tail, much to the shock of Doofenshmirtz and the class. Johnny's head and right arm then mutate to that of a primate's while his left arm mutates to that of a lizard's, and despite being uncomfortable by this, Doofenshmirtz states this as an example of his statement of how the human DNA is only a few base pairs away from primate DNA and reptile DNA. The mutated Johnny then panics and runs out from the classroom into the hallways.
Spotting the panicking Johnny running down the hallways through the school's surveillance systems, Carl informs Major Monogram, who decides to call in Agent P to investigate the issue. As Perry heads over to Danville High, Doofenshmirtz suddenly realizes that he may use the hair sample to formulate a proper antidote to turn Johnny back to normal and convinces the class to help him out. As Perry arrives, several kids wonder if he's really Johnny becoming more mutated than usual, only for Doofenshmirtz to retort that "Mr. Platypus" just came to help. Doofenshmirtz convinces Perry to help him catch Johnny so that he can administer the antidote to turn Johnny back to normal. Doofenshmirtz then assigns Vanessa, Lacie, and two other kids to help Perry catch Johnny while he and the rest of the class can start preparing the antidote.
After going through the hallways, Perry and the kids track down Johnny to the school gym, where he is hiding behind the bleachers. Vanessa attempts to calm him down, assuring that everything will be okay once her father administers the antidote. However, Johnny is scared of an arriving Perry and bursts out from the gym, taking Vanessa with him. Perry attempts to fire a net at Johnny to stop him, but it only catches his reptilian tail. Johnny then runs out from the school building with Perry and the other teenagers on pursuit.
In the meantime, the talking insects (having got themselves out from the beaker) are now sitting on the trash can next to the table, making notes of how they should introduce themselves to the humans. They suggested that they use a welcoming banner to do so. However, one of the students opens the trash can to dispose some garbage, sending the insects to fall back into the floor. Around the same time, the antidote is finally finished, and Doofenshmirtz injects it on a syringe, hoping that the event will blow off once it's injected into Johnny. However, he and the class spot Johnny running outside and climbing onto the bell tower, taking a hostage Vanessa with him.
As Doofenshmirtz and the class head outside to the bell tower, Vanessa complains about Johnny being a drama queen for claiming 'sanctuary'. After Doofenshmirtz gets a crossbow from Becky to help him fire the syringe, Perry lends his hovercraft to help Doofenshmirtz fly up to the tower to get a better shot. Despite their efforts, Johnny avoids them and throws down one of the school bells onto the hovercraft, trapping Perry inside, much to Doofenshmirtz's dismay. The reverberated sound of the fallen bell start to alert Principal Lang, who decides to go find out what's going on.
Meanwhile, at John P. Tristate Elementary School, Sally watches as Phineas and Ferb work on their latest project: making new improvements to the school's playground during recess. Phineas and Ferb then briefly spot Doofenshmirtz flying the hovercraft around the bell tower to get a clear shot at Johnny. This makes Phineas eager about going to high school. As Doofenshmirtz tries to get the bell off from the hovercraft, he finally gets himself a clear shot. However, Perry throws the bell off the hovercraft, accidentally throwing off Doofenshmirtz as well, much to his dismay. Fortunately, the bell lands onto the lawn for Doofenshmirtz to land on, causing him to fire the syringe up into the air. Taking the opportunity, Vanessa catches the syringe and injects the antidote onto Johnny's arm, turning him back to normal. However, Johnny and Vanessa start to fall from the bell tower, but Perry saves them both by using the same net he attempted to capture Johnny with. Johnny thanks Vanessa for saving him, but she warns him (to no avail) not to take this as a sign that she's going back to him. With the trouble finally over for good, Doofenshmirtz and the kids head back to their classroom while Perry goes home. Upon going outside and seeing the fallen bell on the school lawn, Principal Lang then wonders what has happened.
Back in the classroom, the talking insects finally made it to the top of the table, so they present out their own banner to greet the humans. However, Napoleon is annoyed to learn that Wendell and Floyd have misspelled their banner "Welcome Giants" with "Weclom Ginats". As an angry Napoleon berates the two, the insects are then squashed by Doofenshmirtz's Evil Science 101 book, just as Doofenshmirtz finally concludes his genetics lecture to the students. At that point, Principal Lang bursts in, believing that he caught Doof doing something suspicious, only to find out that everything is normal just the way it is. The bell rings for the end of the day, and Doofenshmirtz dismisses the students, who are somewhat impressed by the experience that Doofenshmirtz has brought to them as they leave. This also leaves Lang upset, sulking over his failure to catch Doofenshmirtz doing anything evil. As Vanessa finally warms up to her father being her teacher, she asks if any more of the incidents such as this are to happen again, to which Doofenshmirtz replies that he'll try his best to avoid them, much to Vanessa's relief. As Doofenshmirtz and Vanessa leave the classroom, the talking insects (having survived the book squash) move themselves out from the book, with Napoleon stating that he has broken his exoskeleton and Wendell exclaiming that he just 'bivouacked'.
- When Vanessa and Lacie are talking before class starts, in one of the scenes Lacie's dress is black rather than red.
- When Doofenshmirtz is about to get onto Perry's hoverjet, he is wearing his outfit with a green shirt and purple tie, but when he is on Perry's jet, the outfit changes to his usual black shirt.
- The calendar during the "Doof 101" song shows July ending on a Wednesday, August starting on a Tuesday and ending on a Thursday, and September starting on a Sunday. Additionally July 31st is missing.
- John P. Tristate is misspelled as "John P. Trystate".
- At one point in the background, the chalk board says that the square root of 42 minus 2 plus 1 is equal to infinity, which is obviously not true.
- At the end of the episode, despite it being the end of the school day, the clock next to the blackboard claims it is 9:00.
- April 2014 (New Zealand)
- May 15, 2014 (PlusPlus, Ukraine)
- July 25, 2014 (Disney XD Germany)
- October 19, 2014 (Disney Channel Germany)
- October (Disney Channel Taiwan)
- November 19, 2014 (Spain. On DVD)
- November 28, 2014 (Poland. On DVD)
- January 10, 2015 (Disney XD Poland)
- January 25, 2015 (Disney XD Canada)
- February 15, 2015 (RCTI Indonesia)
- February 26, 2015 (Disney XD UK/Ireland)
- March 19, 2015 (Disney Channel Spain)
- March 28, 2015 (Disney Channel Portugal)
- May 9, 2015 (Disney Channel Asia)
- June 13, 2015 (Disney Channel Latin America)
- July 6, 2015 (Disney Channel Hungary & Czech Republic)
- July 18, 2015 (Disney XD Latin America)
- August 4, 2015 (Disney XD Australia)
- April 22, 2016 (Disney Channel Poland)
- Johnny is climbing up the school bell tower while taking Vanessa with him, similar to how King Kong climbs up the Empire State Building, taking Ann Darrow with him, making it the second time this movie is parodied after "Attack of the 50 Foot Sister".
- Doof sings there are 261 days until next summer vacation to the tune of the show's title sequence of the show. 365 minus 104 is equal to 261.
- This episode takes place while the characters are at school.
- The title of this episode is based on the old Doofenshmirtz's class, Evil 101.
- This marks the first episode to portray talking animals, in this case the bug trio.=
- Phineas and Ferb's school, John P. Tristate Elementary, is named after the Tri-State Area founder, John P. Tristate.
- The calendar says that September the 1st is a Sunday. This suggests it takes place in 2013, as the 2013 calendar marks said date as a Sunday. Dan Povenmire, however, has denied it.
- Ballast is basically another word for "counterbalance". "Bivouac" means making camp.
- This episode was written as a potential spin-off of the show
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