In 1985, Oprah co-starred in Steven Spielberg's epic film adaptation of Alice Walker's Pulitzer Prize-winning novel The Color Purple. She earned immediate acclaim as Sofia, the distraught housewife. The following year Winfrey was nominated for an Academy Award for Best Supporting Actress, but she lost to Anjelica Huston. The Color Purple has now been made into a Broadway musical and opened late 2005, with Winfrey credited as a producer.

In October 1998, Winfrey produced and starred in the film Beloved, based upon Toni Morrison's Pulitzer Prize winning novel of the same name. To prepare for her role as Sethe, the protagonist and former slave, Winfrey experienced a 24-hour simulation of the experience of slavery, which included being tied up and blindfolded and left alone in the woods. Despite major advertising, including two episodes of her talk show dedicated solely to the film, and moderate to good critical reviews, Beloved opened to poor box-office results, losing approximately $30 million. Working with delicate subjects, Winfrey managed to keep the cast motivated and inspired. "Here we were working on this project with the heavy underbelly of political and social realism, and She managed to lighten things up", said costar Thandie Newton. "I've worked with a lot of good actors, and I know Oprah hasn't made many films. I was stunned. she's a very strong technical actress and it's because she's so smart. She's acute. She's got a mind like a razor blade."

In 2005, Harpo Productions released another film adaptation of a famous American novel, Zora Neale Hurston's Their Eyes Were Watching God (1937). The made-for-television film Their Eyes Were Watching God was based upon a teleplay by Suzan-Lori Parks, and starred Halle Berry in the lead female role.