John Dolittle, a respected medical doctor living in the small English town of Puddleby-on-the-Marsh, gradually loses his human clientele because his house is overrun with animal pets, including a duck, a dog, a pig, an owl, and a parrot named Polynesia. Polynesia teaches the Doctor the secret languages of animals, enabling him to understand and cure creatures from all over the world, which brings him immense fame among beasts but leaves him penniless. When a swallow brings an urgent message that a terrible sickness is killing the monkeys in Africa, Dolittle resolves to answer the call despite having no money for the journey. A local sailor lends him a boat, and accompanied by a select group of animal friends, the Doctor sets sail across the ocean.
After surviving a shipwreck, the travelers reach the shores of Africa, where they encounter the King of the Jolliginki. Initially imprisoned for trespassing, the Doctor escapes through the clever ruses of Polynesia. Deep in the jungle, Dolittle successfully treats thousands of sick monkeys with the reluctant help of the local lions, leopards, and antelopes.
Grateful for his service, the animals search the deep jungle to find him a unique parting gift, ultimately capturing the extremely rare, two-headed pushmi-pullyu. On the homeward voyage, the Doctor and his companions face new perils, including capture by Barbary pirates. Dolittle outwits the pirates, strands their leader on an island to farm bird-seed, and rescues a shipwrecked boy's lost uncle who has been surviving on snuff. Returning home a wealthy man through the exhibition of the pushmi-pullyu, the Doctor finally settles back into his beloved house in Puddleby, having forever bridged the worlds of humans and animals.
