Family
- great-great-grandmother Louisa Lane Drew: First woman theater manager in USA
- great-great-grandfather John Drew:
- great-grandfather Maurice Barrymore: Born in 1847; popular stage actor and matinee idol; died of syphilis in 1905
- great-grandmother Georgianna Drew: Born in 1855; died in 1893
- great-grandfather Maurice Costello: Known as 'The Dimpled Darling'; was one of the first matinee idols of the screen
- grandfather John Barrymore: Born in 1882; highly acclaimed matinee idol of stage and screen in the 1920s and 30s; known as 'The Great Profile'; died in 1942
- grandmother Dolores Costello: Popular star of silent films who made a memorable comeback in "The Magnificent Ambersons" (1942)
- great-uncle Lionel Barrymore: Born in 1878; famed, prolific actor who worked primarily in Hollywood over the course of his lengthy career; Oscar winner as Best Actor for "A Free Soul" (1931); died in 1954
- great-aunt Ethel Barrymore: Legendary stage performer who in her later years played character roles in Hollywood films; Oscar winner as Best Supporting Actress for "None But the Lonely Heart" (1944)
- great-aunt Helene Costello: Sister of Dolores Costello, also a silent screen star
- aunt Diana Barrymore: Born in 1920; died in 1960
- father John Barrymore Jr: Born June 4, 1932; separated from Barrymore's mother before her birth, they divorced in 1984; was estranged from daugther for most of his life; died of cancer on Nov. 29, 2004 at age 72
- mother Ildiko Jaid: Separated from Barrymore's father before her birth; they divorced in 1984; posed for Playboy magazine in September 1995, eight months after her daughter did in January 1995; mother and daughter have a strained relationship
- half-brother John Blyth Barrymore: Born in 1954; son of John Barrymore and Cara Williams
- half-sister Blyth Dolores Barrymore: Born in 1962; daughter of John Barrymore and Gabriella Palazzoli
- half-sister Jessica Barrymore: Older; daughter of John Barrymore and Nina Wayne
- godmother Anna Strasberg:
Companions
- Companion Spike Jonze: Dated for a few months in 2007; no longer together
- Companion Luke Wilson: Worked with Barrymore in "Best Men" (1997) and "Home Fries" (1998); together from 1996-1999
- Companion Justin Long: Met on the set of "He's Just Not That Into You" (2009); began dating in August 2007 and split in July 2008; began dating again in early 2009
- Companion Alex Piro: Dated in 2002; no longer together
- Alec Pure: born c. 1976
- Brandon Davis: dated April 2002
- Eric Erlandson: born c. 1963; guitarist with the rock group Hole (featuring Courtney Love); Barrymore nicknamed him 'String Bean' (he stands 6'4"); no longer together
- Fabrizio Moretti: dated May 2002; no longer together as of September 2002; reconciled in October 2002; rumored to be engaged as of January 2003
- James Walters: born in July 1969; announced one-year engagement in August 1992; separated in January 1993
- Jeremy Davies: briefly dated in early 1999
- Joel Shearer: dating as of September 2002
- Luke Wilson: born c. 1971; worked with Barrymore in "Best Men" and "Home Fries"; together from 1996 to 1999
- Phedon Papamichael: together c. 1992; no longer together
- Val Kilmer: involved c. 1995; Barrymore has said they were only friends
