During a rousing nine-minute address, the talk show host touched on women’s rights, the importance of a free press and what it meant to be the first black woman to receive the prestigious Cecil B. DeMille Award.
Before receiving a standing ovation, she closed with the promise “a new day is on the horizon”, adding fuel to rumours the entertainment mogul could have her eyes on the White House.
She said: “A new day is on the horizon. And when that new day finally dawns, it will be because of a lot of magnificent women, many of whom are right here in this room tonight, and some pretty phenomenal men, fighting hard to make sure they are the leaders to take us to the time where nobody has to say ‘me too’ again.”
She also offered her support the “under siege press” and praised the efforts of reporters for their “dedication to uncovering the absolute truth that keeps us from turning a blind eye to corruption and to injustice.”
In response to her remarks, social media users were quick to support a possible presidential bid by the 63-year-old with many seeing her comments has an opening salvo to a possible presidential campaign.
Taking to twitter, one user wrote: “Oprah went from being dirt poor to becoming an ACTUAL self made billionaire, is intelligent, empathetic, hardworking & has done so much humanitarian work on top of being one of the best communicators on earth, why SHOULDN’T she run for president?! #Oprah2020.”
Another tweeted: “Humane, inclusive, enlightening, inspiring and eloquent. It’s been a while, but this is what a leader is supposed to sound like, right? #Oprah2020.”
Another user said: “The only way Oprah’s speech would have been more perfect was if she announced at the end that she was running for President.”
The TV star has previously played down her presidential ambitious, insisting in June last year she “pretty definitely will never run for public office”.
Though her high-profile, popularity and affiliation with the Democratic Party could make her the ideal candidate to stand against Mr Trump in 2020, whose low approval ratings have made him the least popular President in modern history.
The real estate mogul, 71, has made it clear he intends to run for a second term, going as far as submitting the paperwork for his 2020 re-election campaign on the day of his inauguration.
However much of his first year in office has been dogged by an ongoing investigation into possible collusion between members of his campaign and Russian agents which has already seen several members of his team plead guilty to lying to the FBI.
And despite a booming economy, and a sweeping overhaul of the US tax system, Mr Trump has failed to pass much else in the way of major legislation.