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 with strangely bestial festures, the captain tosses Parker overboard into Mr. Montgomery (Arthur Hohl) and Moreau's boat.
When Parker arrives at his island, 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 resembling apes, felines, swine, and other beasts emerging from the jungle. Moreau appears, cracks his whip, and orders the one known as the Sayer of the Law (Béla Lugosi), a wolflike creature, 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 fingernails, with have reverted to animal-like claws. 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, then he despairs, believing that he has failed – until he notices Lota weeping as humans do. 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 in Samoa, 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. The apelike Ouran, one of Moreau's creations, tries to break into Ruth's room. (It is implied that this is arranged by Moreau, who is eager to see if his beast-men can successfully mate with humans.) 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. Reverting to their animal nature, they set their huts ablaze and defy Moreau, who tries to regain control with his whip, but to no avail. In desperation, he demands of them, "What is the law?" Their response is, "Law no more!" The beast-men drag the doctor into his House of Pain, where they bind the screaming man to the operating table and destroy him 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 escape by boat as the island goes up in flames, presumably destroying all of Moreau's work and eradicating the beast-men.
The film was examined and refused a certificate three times by the British Board of Film Censors, in 1933, 1951, and 1957. The reason for the initial ban was due to scenes of vivisection; it is likely that the Cinematograph Films (Animals) Act 1937, which forbade the portrayal of cruelty to animals in feature films released in Britain, was a significant factor in the BBFC's subsequent rejections. The film was eventually passed after cuts were made with an 'X' certificate on July 9, 1958. It was later classified as a PG on DVD in 2011 with the cuts reinstated.
Among the BBFC's objections were references to vivisection and "cutting a living man to pieces", and Dr. Moreau saying "Do you know what it means to feel like God?"
Original author H. G. Wells was outspoken in his dislike of the film, feeling the overt horror elements overshadowed the story's deeper philosophical meaning.
The film is the source of the saying "The natives are restless tonight." The actual dialogue is as follows:
Ruth Thomas (hearing chanting): "What's that?"
Dr. Moreau: "The natives, they have a curious ceremony. Mr. Parker has witnessed it. "
Ruth Thomas: "Tell us about it, Edward. "
Edward Parker: "Oh, it's... it's nothing. "
Dr. Moreau: "They are restless tonight."
Two films have since been made based on the same H. G. Wells novel. The first was released in 1977 and stars Burt Lancaster as the doctor. The second came out in 1996, with Marlon Brando as Moreau. In the very similar The Twilight People (1973), actress Pam Grier played the panther woman.
Playwright Charles Ludlam used this movie, as well as Wells' novel and the fairy tale by Charles Perrault, when writing his play Bluebeard (1970).
Members of the new wave band Devo were fans of the film. The "What is the law?" sequence formed part of the lyrics to Devo's song "Jocko Homo," with Lugosi's query "Are we not men?" providing the title to their 1978 debut album Q: Are We Not Men? A: We Are Devo! Devo's short film "The Truth About De-Evolution" and an interview with founding members Gerald Casale and Mark Mothersbaugh are special features on the Criterion Collection release of the film.
Oingo Boingo is another new wave band who paid tribute to the film with their song "No Spill Blood," which featured the refrain "What is the Law? No spill blood!" and appeared on their 1983 album, Good for Your Soul.
The Meteors, a psychobilly band from the UK told the story of the film in their song "Island of Lost Souls" on their 1986 album Teenagers From Outer Space, the chorus being a prolonged chant of "We don't eat meat; Are We Not Men? We stand on two feet; Are We Not Men?" etc.
Heavy metal band Van Halen paid homage to the film in the original version of their song "House of Pain", the early lyrics for which directly referenced the storyline of the movie. During onstage introductions of the song circa 1976-77, Van Halen vocalist David Lee Roth routinely gave a brief synopsis of the film. The song was shelved for the better part of a decade, but eventually resurfaced with different non-movie-related lyrics and released on the band's 1984 album.
The US horror-rock band Manimals based much of their stage persona on the film. Their 1985 Blood is the Harvest vinyl E.P. closes with the song "Island of Lost Souls". The track includes a "What is the Law?" section that fans would chant during live shows. The film historian Gary Don Rhodes has called them "the best-ever in the horror-rock genre" and referenced them in his 1997 book Lugosi (McFarland Press).