The Oprah Winfrey Show is a popular syndicated daytime talk show hosted by Oprah Winfrey. It holds the record for the longest running daytime talk show in America.
- 1997 -- Big Bird, Rosita, Elmo, and Zoe appear on the show to promote children's literacy by promoting various books such as the works of Richard Scarry, Make Way for Ducklings, and Another Monster at the End of This Book.
- November 19, 1998 -- Big Bird and Baby Bear appear in a pre-taped segment at Big Bird's nest to give a special birthday greeting for the McCaughey septuplets, counting each of them in the order they were born (underscored with an instrumental version of the Sesame Street Theme from the 30th season). Bear later appears in a separate video to give a birthday greeting, then does a "First Birthday Cha-Cha" dance.
- May 19, 2003 -- Oprah viewer Mona, a schoolteacher from Detroit, writes in to the show asking to be granted a set visit to Sesame Street. Her wish is granted as an Oprah filming crew accompanies her to New York City where she meets and speaks with Elmo, Cookie Monster, Ernie, Big Bird, The Two-Headed Monster (who is dressed for the segment "Journey to Big Bird", Episode 4058), Grover and Zoe.
- February 27, 2006 -- Kevin Clash makes a short appearance in what is advertised in the show's bumpers as one of his few on-screen appearances without Elmo. (A few months later, Clash makes a lengthier solo appearance on Rove Live, briefly referencing this appearance.)
- Statler says that Oprah hosts the best talk show on TV, after an opera number at the Royal Variety Performance.
- In Elmo's Christmas Countdown, Stiller the Elf is upset that he may have prevented Christmas from coming, and he is seen talking to himself, justifying how it happened. He says that he's merely practicing for when he has to apologize to the world on Oprah.
- Tom Cruise's notorious appearance on The Oprah Winfrey Show was spoofed in an episode of Statler & Waldorf: From the Balcony, with Tom Cruise jumping up and down during an interview with Loni Dunne, accidentally kicking her head off.
- In Miss Piggy's Rules, Miss Piggy suggests taping your favorite Oprahs over your boyfriend's collection of Star Trek episodes.