In early Victorian period, Matthew Mugg (Anthony Newley) takes his young friend Tommy Stubbins (William Dix) to visit eccentric Doctor John Dolittle (Rex Harrison) for an injured duck that Matthew had acquired from a local fisherman. Dolittle, a former medical doctor, lives with an extended menagerie, including a Common chimpanzee named Chee-Chee, a dog named Jip, and a talking parrot named Polynesia (the uncredited voice of Ginny Tyler). Dolittle claims that he can talk to animals. In a flashback, he explains that he kept so many animals in his home that they created havoc with his human patients, who took their medical needs elsewhere. His sister, who served as his housekeeper, demanded that he dispose of the animals or she would leave; he chose the animals. Polynesia taught him that different animal species can talk to each other, prompting Dolittle to study animal languages so that he could become an animal doctor. He is planning his latest expedition: to search for the legendary Great Pink Sea snail.
A few years after the events of the Dr. Dolittle (film), Dr. John Dolittle's (Eddie Murphy) work as a veterinarian who can talk to animals has made him famous, and he often takes trips around the world to perform his skills. One night, John comes home from France and gives his wife a present from Paris. He also gives his daughter, Maya (Kyla Pratt), a chameleon named Pepito (voice of Jacob Vargas). Also, Charisse's (Raven-Symoné) sixteenth birthday is coming today, but she is also not doing well in her classes. As a punishment, John takes her phone away. Later on, Charisse's boyfriend, Eric (Lil Zane), comes over and decides to join the family at the birthday party. During all this, a opossum (voice of Isaac Hayes) and a raccoon, Joey (voice of Michael Rapaport), approach John and tell him that their boss, the Godbeaver, wants to see him. The next day, John meets the God beaver (voice of Richard C. Sarafian), who shows him that the forest is being cut down. John plans to save the forest by getting an endangered female Pacific western bear together with a male to save their species.
