The 63-year-old, who yesterday became the first African- American woman to win the Cecil B DeMille Award at Golden Globe Awards 2018, used the platform to say that discrimination based on race and gender was no longer acceptable.
Two of her close friends told CNN on condition of anonymity that some of her trusted people had been urging her to run for the post and she was "actively thinking" about it.
At the Golden Globes ceremony yesterday, host Seth Meyers rooted for Winfrey's electoral debut in his opening monologue itself.
"In 2011, I told some jokes about our current president at the White House Correspondents Dinner, jokes about how he was unqualified to be president. And some have said that night convinced him to run. And if that's true, I would just like to say, 'Oprah, you will never be president'.
"And Hanks! Where is Hanks? You will never be vice president! You are too mean and unrelatable. Now we just wait and see," he joked.
Fellow actor Alyssa Milano tweeted her response to a link hinting at Winfrey's possible political plunge, "Yes, please @Oprah. Yes."
Declaring his support, British celebrity chef Jamie Oliver started a mini presidential campaign on Instagram and said it would be "the biggest landslide victory in the history of America" if Winfrey runs for the office.
"I've got a strong feeling this woman should be the next President of the United States of America. She'd get my vote. It would be the biggest land slide victory in the history of America," Oliver wrote alongside a photograph of Winfrey with 'OPRAH 2020' written at the bottom.
"Given the choice between Oprah and our current president, I'm on the bus with Oprah traveling the country encouraging people to sign up and vote. We'd have to call her President Winfrey, you realize that? I don't know if we're prepared for that as a country," Kimmel told reporters at the Television Critics Associations press tour in Pasadena, California.
In her widely-praised speech Globes speech, Winfrey said Sidney Poitier, the first African-American man to win the Best Actor Oscar for "Lilies of the Field" and the Cecil B DeMille honour, inspired her as a little girl.
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