Having done his best to keep Buddy buried in his subconscious, the portly and painfully shy professor is horrified to find him resurfacing in untimely outbursts, and threatening his marriage plans to colleague Denise Gains. Utilizing Denise's cutting-edge DNA research, Sherman decides to rid himself of his monstrous nemesis--and his disruptive outbursts--once and for all by extracting Buddy's DNA from his system. But Buddy will not go quietly. He bursts full-bodied into Sherman's world and lays claim to the professor's astounding invention--a revolutionary youth serum. The serum can turn back time temporarily, shave decades off one's appearance and restore vitality, making it a hugely lucrative property that everyone's clamoring for. Desperate to keep it from Buddy, Sherman hides the serum in the Klump family home, thinking it will be safe. But Buddy finally locates the lucrative "youth juice," and steals away. And so begins a race against time, as Sherman battles to reclaim his formula, restore order to his family, and marry the woman he loves before all hell breaks loose.