Monkey encounters Simion (Maurice LaMarche), an intelligent anthropomorphic chimpanzee who seeks vengeance on humans for turning him into his current state.
In need of an assistant to operate his latest invention, Dexter performs a brain transplant on Dee Dee to make her smart enough to fulfill the role. With her new brain, Dee Dee proves to be more intelligent than Dexter.
Dexter is forced to take Dee Dee to the zoo. There, she ends up trying to save an ostrich with disastrous results. Dee Dee and the ostrich switches their places.
Dee Dee dares Dexter into building her a giant robot similar to his Robo-Dexo 2000. They then team up to try to save an island’s population from being destroyed by an erupting volcano using their giant robots.
In a parody of Tom and Jerry, Dexter accidentally switches his brain with that of a mouse’s and must avoid his mother when she decides to exterminate him.
Dexter, Monkey, Agent Honeydew, the Justice Friends, Dee Dee, her imaginary friend Koosalagoopagoop, Mandark, his parents, and Dexter’s parents participate in a cross-country race a la Wacky Races.
Monkey’s birthday party is interrupted by Barbequor (Robert Ridgely), an intergalactic villain who plans to eat the planets, and his sidekick, the Silver Spooner (Rob Paulsen).
Dexter’s parents discover that he is making false excuses to get out of physical education and now Dexter must pass a physical exam if he wants to pass P.E. and move up a few grades.
When Dexter is asked to bring his mother to school, he disguises Dee Dee as her so that she can take her place, but Dee Dee does not behave like their mother.