Lillian Hellman adapted The Little Foxes into a screenplay in 1941 that starred Bette Davis as Regina and won critical acclaim for director William Wyler and cameraman Gregg Toland, later famed for his deep-focus camerawork in Citizen Kane. The black-and-white film was nominated for nine Academy Awards, but received none.

In 1949 Marc Blitzstein premiered an opera adaptation called Regina with original libretto and music. Although it ran for only a few months, it fared better than the usual Broadway opera.

An NBC television drama based on the play was broadcast in 1956, and starred Greer Garson. It was produced by George Schaefer, with a screenplay by Robert Hartung, and was broadcast as an episode of "The Hallmark Hall of Fame" series.