Lance Perkins, portrayed by Eddie Murphy, serves as the charismatic host of a television exercise program aimed at helping overweight individuals. In contrast, Professor Sherman Klump, also played by Eddie Murphy, is a gentle, well-respected, and brilliant genetics professor getting ready for his day at Wellman College. Chaos is in the air as 5,000 lab hamsters are currently creating mayhem across the campus, stemming from a mishap where Sherman, in a rather unfortunate accident involving his considerable girth, accidentally released them by bumping the cage latch.
As the mayhem unfolds and the hamster crisis is eventually managed, Sherman receives a well-timed update from his assistant, Jason (John Ales), concerning their groundbreaking project: an experimental formula that can alter the DNA of heavier individuals to facilitate weight loss. The glimmers of hope from their research shine bright, especially when they discover that their largest test subject, a hamster named Shelley, has lost a significant amount of weight — a whopping three ounces! However, despite Jason's suggestion to increase Shelley's food intake, the ever-kind-hearted Sherman advocates caution, worrying that it might pose risks to the creature's health.
The pressure mounts further when Dean Richmond (Larry Miller) meets with Sherman to inform him that the recent hamster incident has cost the science department a substantial amount of its funding. Harlan Hartley (James Coburn), the college's benefactor, is the last wealthy alumnus who may consider donating a generous $10 million grant, but the Dean insists that Sherman must tread carefully in order not to offend him.
After classes, Sherman encounters the alluring Miss Carla Purty (Jada Pinkett), a fellow chemistry grad student who expresses admiration for his work. This serendipitous meeting causes an instant spark of romance for Sherman, bringing to life feelings he hasn’t experienced in a long while. However, family dinners pose another set of challenges; his boisterous and ill-mannered relatives, whom Eddie Murphy masterfully embodies, often mock him for his weight. In a comical yet revealing exchange, the family's remarks leave Sherman feeling vulnerable, but his mother Anna reminds him that he is “beautiful inside and out,” encouraging him to pursue his heart’s desire.
Motivated by his feelings for Carla, Sherman is determined to shed some pounds and seeks the energy to support his goal after drifting into a dream inspired by Lance Perkins' motivational TV appearance. With earnest determination, Sherman embarks on a comedic, Rocky-style montage filled with crazy exercise attempts, hoping to prepare for his upcoming date. Unfortunately, their delightful evening takes a turn for the worse when Reggie Warrington (Dave Chappelle), a ruthless comedian, begins to target Sherman with his harsh jests about obesity. Embarrassed and in tears, Sherman must cut their date short, leaving Carla furious at Reggie’s cruelty.
In a state of despair, Sherman finds himself bingeing on junk food while watching Lance Perkins offer uplifting words to another overweight individual. This moment triggers a surreal nightmare where he imagines transforming into a monstrous giant, wreaking havoc in a comical fashion that ultimately leads him to succumb to the temptation of the experimental serum, which he decides to try on himself. Almost instantaneously, Sherman undergoes an incredible transformation, shedding three hundred pounds to reveal a leaner physique brimming with confidence. Thrilled by his newfound appearance, he buys stylish clothes and enthusiastically embraces an energetic lifestyle.
Buoyed by his success, Sherman begins to flirt with Carla, inventing the persona of “Buddy Love” to capture her attention. This new identity allows him to woo Carla more effectively; however, the serum’s effects start to fade unexpectedly, complicating his romantic endeavors. When Buddy arrives late to pick Carla up in a sleek Dodge Viper, the evening spirals into chaos, with Reggie attempting to deliver his usual insults. But Buddy stands his ground, turning the tables, showcasing strength and charisma that leaves Reggie stunned.
As Buddy's antics take a darker turn, the complexity of his character becomes apparent — he’s not simply an improved version of Sherman but a wild, uncontrolled personality vying for dominance. As the night of the college alumni ball approaches, Sherman's clash with Buddy reaches a fever pitch. Ultimately, their intense battle culminates in a shocking realization for Sherman: the most critical victory lies in self-acceptance rather than the pursuit of external validation.
Standing in front of the alumni audience, Sherman passionately conveys how he once sought to help others but, in doing so, lost sight of what was truly important - his self-acceptance. As Carla engages him with an invitation to dance, it symbolizes a promising new chapter for them both. Amidst applause and newfound recognition from Hartley for his scientific brilliance, Sherman begins to find his footing, letting go of past insecurities to embrace who he truly is, both inside and out.
