Jim Carrey as Lloyd Christmas, one of the two protagonists; a semi-literate and mischievous man who has been fired from several jobs due to his lack of intelligence and his unwillingness to work "40 hours a week," the most recent of which is driving a limousine. He melodramatically falls in love with Mary while taking her to the airport, and becomes convinced he is destined to track her down, return her misplaced briefcase, and spend his future with her.
Jeff Daniels as Harry Dunne, one of the two protagonists; a good-natured dog groomer, and best friend to Lloyd. What he lacks in common sense, he makes up for by being a superior linguist to Lloyd. With Lloyd, he plans to open up his own pet store to specialize in selling worm farms; the store is tentatively named "I Got Worms."
Lauren Holly as Mary Swanson, an attractive woman whose husband, Bobby, has been kidnapped (by a family friend, it is ultimately revealed). She is the object of Lloyd's longing, and when Harry meets her, she also becomes the object of Harry's longing.
Charles Rocket as Nicholas Andre, the main antagonist; the polar opposite of Lloyd and Harry, Nicolas Andre is a wealthy, handsome, intelligent and upper-class resident of Aspen, Colorado, who enjoys fine living. Andre is a long-time confidant of the equally wealthy family of Aspen, the Swansons; however Andre is behind the plot to kidnap Bobby Swanson and demand a ransomthrough third parties. His plot is unwittingly foiled by Harry and Lloyd after they find and spend the ransom money, drawing the attention of the FBI. After attempting to kill Lloyd and Harry, Andre is arrested.
Mike Starr as Joe "Mental/Gas-Man" Mentalino, the secondary antagonist; a tall, beefy, cold-hearted criminal who works as a henchman for Nicholas Andre, the kidnapper. He suffers from severe digestive problems, including ulcers and intestinal gas, for which he is continually seen popping prescription antacid pills. He attempts to kill Lloyd and Harry, as well as retrieve the briefcase, but is accidentally killed for his troubles when the rat poison tablets (with which he intended to poison Lloyd and Harry) are mistaken for his pills (which Harry and Lloyd tried to feed him after they, unaware of his condition, loaded a burger with extremely hot chili peppers). He is increasingly angered by the idiocy of Lloyd and Harry.
Karen Duffy as J.P. Shay, Mental's female accomplice. She appears as Andre's date at the wildlife benefit. She is arrested with Andre by the FBI at the end of the film.
Victoria Rowell as Beth Jordan, an FBI agent masquerading as a talkative young woman who is moving to Aspen to get away from her clumsy boyfriend. She is actually following Lloyd and Harry as she is investigating the kidnapping and knows they have the ransom money. She befriends Lloyd in a bar as he expects to meet with Mary, having previously met Harry as they both refueled their cars at a gasoline station.
Brad Lockerman as Bobby Swanson, Mary's husband and the rich victim of Andre's plot. He is in captivity throughout the film, until the end, when he is freed.