As she received a lifetime achievement award from the Hollywood Foreign Press Association, the actress and TV star spoke of her humble upbringing and her childhood respect for civil rights heroes.
Trump had once cited Winfrey as his choice for a running mate when he was toying with running for the Reform Party presidential nomination for the 2000 election.
Maria Shriver, the former wife of Arnold Schwarzenegger, said she was "proud" of Winfrey, adding: "A new day is on the horizon".
"So when I chose to talk with you, people around me were like, 'What's happened to you?'" she continued. "We welcome the challenge, whether it be Oprah Winfrey or anybody else", Hogan Gidley told reporters on Air Force One during a flight to Nashville on Monday.
The nine-minute speech generated two standing ovations from the Hollywood glitterati and prompted 220,000 posts on social media mentioning the words "Oprah" and "president" in just 24 hours, said Todd Grossman of social media analytics company Talkwalker.
Actor Josh Gad wrote: "Can we all agree that Oprah deserves a planet named after her". She is credited with roles in almost 30 movie and TV productions, including a role in director Steven Spielberg's The Colour Purple that earned her an Oscar nomination for best supporting actress.
"I want to express gratitude to all the women who have endured years of abuse and assault because they, like my mother, had children to feed and bills to pay and dreams to pursue". Yes it is. May we all greet it with hope, resolve and faith. I'm assuming she'd run as a Democrat, since that's where her worldview and sensibilities best fit.
Mayers referenced in his opening monologue comments he had made about current United States president Donald Trump during the 2011 White House Correspondents' Association Dinner. Magnificent speech, magnificent career, magnificent woman! Winfrey made her first campaign appearances on Obama's behalf in December of that year, and it is logical to assume that her support won him votes in the primaries, though it is not possible to know how many.
Winfrey endorsed Democratic Senator Barack Obama of IL when he first ran successfully for the U.S. presidency in 2008, and former U.S. Secretary of State Hillary Clinton in her losing 2016 campaign against Trump.