In the 1930s and 1940s, Lionel Barrymore starred in a series of Doctor Kildare movies. He played:

During the 1930s and 1940s, he became stereotyped as a grouchy but sweet elderly man in such films as The Mysterious Island (1929), Grand Hotel (1932, with John Barrymore), Captains Courageous (1937), You Can't Take It with You (1938), On Borrowed Time (1939, with Cedric Hardwicke), Duel in the Sun (1946), and Key Largo (1948).

In a series of Doctor Kildare movies in the 1930s and 1940s, he played the irascible Doctor Gillespie, a role he repeated in an MGM radio series that debuted in New York in 1950 and was later syndicated. He also played the title role in the 1940s radio series, Mayor of the Town. Barrymore had broken his hip in an accident, hence he played Gillespie in a wheelchair. Later, his worsening arthritis kept him in the chair.