During the opening credits, animated sequences featuring various animals are accompanied by an orchestral overture, with the standout number being "Talk to the Animals." The narrative unfolds in the charming 19th-century English seaside village of Puddleby-on-the-Marsh. Here, Matthew Mugg, an Irish fishmonger, crosses paths with his young companion, Tom Stubbins, as he maneuvers his fish barrow, gathering fresh seafood for local patrons. In an act of kindness, Matthew rescues an injured duck from a fisherman intent on making it dinner. Once he completes his rounds, he proposes they take the duck to none other than Dr. John Dolittle, the world-renowned animal doctor. Matthew shares how Dolittle possesses the unique ability to converse with animals, enabling him to diagnose their ailments, and elaborates on this notion through the lively song, "My Friend the Doctor."
As they reach Dolittle's house, they are greeted by Chee-Chee, a chimpanzee, and Polynesia, a parrot. In the library, they find Dr. Dolittle engaged in conversation with some goldfish about the mystical Great Pink Sea Snail, planning an expedition to locate this legendary creature. After a comical exchange and revealing that the duck has been feuding with its mate, Dolittle invites Matthew and Tom to dinner, enlisting Polynesia to prepare for their arrival. The duo, who faced a thunderstorm on their way, is provided with dry clothes by Dolittle. As they return, Chee-Chee is frying sausages while a pig squeals in distaste. Dolittle, however, refrains from joining the feast, explaining his vegetarian lifestyle, which he whimsically details in "The Vegetarian."
Reflecting on how he became a veterinarian, Dolittle recounts a humorous flashback to when he was a general physician, struggling to manage his household due to the influx of animals that his sister, Sarah, found increasingly frustrating. This setup brings in notable characters, including Lady Petherington, who visits Dolittle with her mouse-related woes, while the local Vicar and General Bellowes add to the chaos, leading to Sarah issuing an ultimatum. Ultimately, Dolittle chooses to pursue a life with animals at the expense of human relationships, ignited by Polynesia’s urging to become an animal doctor.
With encouragement from his feathered friend, he launches into "Talk to the Animals," expressing his longing to connect with creatures in their terminology. A sequence of optimistic zeal culminates in the revelation that he has already mastered 498 animal languages as he assembles a unique crew for his quest for the Great Pink Sea Snail. Challenges arise with General Bellowes falsely accusing Dolittle of horse thievery, leading to a series of comedic misunderstandings involving various animals and an eccentric horse with oversized glasses.
Emma Fairfax, Bellowes' niece, enters the fray, initially critical of Dolittle's methods but gradually won over by his charm and the beauty of life through Matthew's song, "Beautiful Things." As the adventures unfold, Dolittle helps animals in distress, including a seal named Sophie, whom he assists in reuniting with her mate across the Channel during a daring escapade involving disguise and clever maneuvers, culminating in a humorous court scene where his abilities are put on trial before Bellowes, who thinks he’s lost his mind.
Facing the possibility of confinement in an asylum, Dolittle and his gang plot a daring escape to pursue their nautical journey on the Flounder. Amongst a chaotic turn of events during a storm, they find themselves marooned on Sea-Star Island where Dolittle’s talents as a healer save him from a death sentence after he brings balance back to the island’s ecosystem with the help of a surprisingly educated tribal chief, William Shakespeare, the Tenth.
After a series of antics involving a blue whale and a dramatic escape from the island, Dolittle finally discovers that the Great Pink Sea Snail is within reach. In a heartfelt goodbye to Emma, who hopes to join him on his return home, Dolittle promises to explore the moon on the Giant Lunar Moth. Their destinies align as Sophie, the seal, returns, urging Dolittle back home where the animals of England yearn for their beloved doctor. The film closes with Dolittle, atop the moth, soaring back to his friends, as a chorus of animals joyously celebrates the reunion with a reprise of "My Friend the Doctor."
