Professor Sherman Klump has devised an innovative de-aging formula that has the potential to revolutionize his life. He is romantically involved with DNA researcher Denise Gaines, the mastermind behind a groundbreaking method to isolate genetic material. However, amidst his newfound happiness, Sherman's alter ego, Buddy Love, begins to increasingly dominate his actions, leading to a chaotic incident during Sherman's proposal to Denise that turns into a public spectacle of embarrassment.
Determined to rid himself of Buddy once and for all, Sherman disregards the warnings of his assistant Jason regarding the potential dangers. He uses Denise's pioneering techniques to isolate Buddy's DNA. Unfortunately, an unexpected twist occurs when a hair from Jason's Basset Hound, Buster, inadvertently contaminates the mix, resulting in Buddy becoming a living entity. After apologizing to Denise, the couple becomes engaged. Their joy is interrupted when Dean Richmond announces that Phleer Pharmaceuticals is willing to pay Wellman College a staggering $150 million for the youth formula.
An encounter at a movie theater reveals the reformed Buddy, who takes advantage of Sherman and discovers the lucrative contract. In a bold move, Buddy teams up with Leanne Guilford, the President of Acquisitions, to make a competing offer of $149 million for the youth formula. Meanwhile, Sherman notices troubling changes in himself, including a significant decline in his intelligence due to the problematic extraction, which sparks his urgency to safeguard the youth formula by storing it at his parents' house.
Chaos erupts when Sherman's frustrated father, Cletus, inadvertently consumes some of the youth formula at a nightclub, leading to an awkward seduction attempt with Sherman's mother, Anna, who is repulsed. Buddy seizes the opportunity to figure out the whereabouts of the formula. As Sherman's condition deteriorates, he becomes increasingly embarrassing in front of Denise's parents, much to her dismay.
In a shocking turn of events, Buddy pilfers some of the youth formula from the Klump household, topping it off with fertilizer, which leads to disastrous consequences during a demonstration. There, Petey, the male hamster meant to showcase the formula, mutates into a gigantic creature that wreaks havoc, even assaulting Richmond in the chaos. As a result, an agitated Richmond fires Sherman, who is then confronted by Jason about his deteriorating mental state, prompting him to end his relationship with Denise. In a moment of unexpected wisdom, Cletus comforts Sherman and reveals the secret to restoring his intelligence: he must reintegrate Buddy Love back into his DNA.
Racing against time, Sherman concocts a new, powerful formula while he still possesses some of his cognitive abilities. Richmond mistakenly believes Sherman and Buddy are collaborating and demands an explanation. Sherman hurriedly makes his way to a presentation at Phleer Pharmaceuticals, where Buddy is showcasing the youth formula. Unbeknownst to him, Denise grows increasingly worried about Sherman's swift cognitive decline and decides to act. With Cletus' assistance, she rushes to find him.
In a climactic moment, Sherman utilizes the canine DNA mixed with Buddy's essence to throw a tennis ball, capturing Buddy's attention. In an extraordinary turn, Buddy's consumption of the ball leads to his gradual transformation back into a toddler, ultimately reducing him to a radiant mass of sentient genetic material. Sherman chases after the escaping genetic matter, desperate to reclaim his intelligence, but it evaporates just before he can drink it. Cletus and Denise arrive too late, and when Denise inadvertently sheds tears that touch the glowing genetic material, it rejuvenates, falling into a nearby fountain.
Upon inspecting the fountain water, Sherman remarks in wonder that it looks "pretty." This revelation spurs Denise into action, realizing that the glowing water holds the key to restoring Sherman. He drinks from the fountain, and miraculously, his intelligence is revived. The story culminates in the joyous wedding of Sherman and Denise, while Cletus and Anna rekindle their romance.
