Shipwrecked traveler Edward Parker (Richard Arlen) is rescued by a freighter delivering animals to an isolated South Seas island owned by Dr. Moreau (Charles Laughton). When Parker objects to the freighter's captain (Stanley Fields) mistreating M'ling (Tetsu Komai), an odd-looking passenger, the captain tosses Parker overboard into Montgomery (Arthur Hohl) and Moreau's boat.
Moreau offers Parker the hospitality of his home and introduces him to Lota (Kathleen Burke), a beautiful, gentle girl who seems a bit simple. When the two hear screams coming from a locked room, which Lota calls the house of pain, Parker investigates. He sees Moreau and Montgomery operating on a person without anesthetic. Convinced that Moreau is engaged in sadistic vivisection, Parker tries to leave, only to encounter brutish-looking men emerging from the jungle.
Moreau appears, cracks his whip, and orders the one known as the Sayer of the Law (Bela Lugosi) to repeat the rule against violence. Afterward, the strange men disperse. Back in the main house, the doctor corrects Parker's mistaken impression. Moreau explains that he started experimenting in London many years previously, accelerating the evolution of plants.
He eventually graduated to animals, trying to transform them into people through "plastic surgery, blood transfusions, gland extracts, and ray baths". He would still be working in England on his "bio-anthropological research" if a dog had not escaped from his laboratory and so horrified the people that he was forced to leave. He reveals that Lota is the sole woman on the island, but hides the fact that she is derived from a panther.
Later in private, he expresses his excitement to his assistant, Montgomery, that Lota is becoming more human in her emotions due to her attraction to Parker. To keep Parker around to continue the process, Moreau sees to it that the boat that was to take Parker away is destroyed and places the blame on his beast-men. As Parker spends time with Lota, she falls in love with him.
Eventually the two kiss, but Parker is stricken with guilt, as he has a fiancee, Ruth Thomas (Leila Hyams). When Lota hugs him, Parker feels pain from her three-inch-long claw-like nails. In a fit of rage, he storms into the office of Dr. Moreau and tells him that he considers it criminal to turn panthers into women. Dr. Moreau calmly explains that Lota is his most perfect creation, and he wanted to see if she was capable of falling in love with a man and bearing human-like children.
Parker punches Moreau and orders him to make arrangements for him to leave the island as soon as possible. When Moreau discovers that Parker found out about Lota's nature because she is starting to revert to her panther origin, he despairs, believing he has failed – until he notices Lota crying. His hopes are raised and he screams that he will burn out all the animal in her in the house of pain.
In the meantime, the American consul (George Irving) at Apia, Parker's destination, learns where Parker is from the cowed freighter captain. Ruth persuades Captain Donahue (Paul Hurst) to take her to Moreau's island. She is reunited with Parker, but as it is late, Moreau persuades them that it is too dangerous to return immediately to Donahue's ship. They reluctantly agree to stay the night.
Ouran, one of Moreau's creations, tries to break into Ruth's room. Fortunately, she wakes up and screams for help. Donahue then offers to try to reach the ship and fetch his crew. Moreau, seeing him depart, dispatches Ouran to strangle him. This has an unforeseen effect, however. The beast-men no longer feel bound by Moreau's laws, as he has himself broken one of them.
Moreau tries to regain control with his whip, but to no avail; in desperation, he demands of them, "What is the law?" But their common response is, "Law no more!!!" With that, they drag the doctor into his house of pain, where they stab him to death with his own surgical instruments.
With help from the fed-up Montgomery, Parker and Ruth make their escape. Parker insists on taking Lota with them. When Lota sees Ouran following, she waits in ambush. In the ensuing struggle, both are killed. The others leave, as the island goes up in flames.