Massively obese, yet loving and kind-hearted, professor Sherman Klump is painfully shy and a bit clumsy, so his romantic prospects are rather bleak. Klump is on the verge of a breakthrough in DNA restructuring when he meets an admirer of his, named Carla, who is a new teacher. He then decides to test a formula on which he's been working on himself. Suddenly, Klump is transformed into the slim, trim, and handsome Buddy Love; however, the drug also boosts his testosterone level, turning the likable Sherman into the arrogant, skirt-chasing Buddy.