The 73-year-old star was on the red carpet at the world premiere of his new film "The Comedian" in Los Angeles when he was asked how he was coping with Trump's victory over Democratic rival Hillary Clinton.
"How am I doing? I'm very depressed," the famously laconic "Raging Bull" actor told reporters.
"We have to just wait and see how things go and keep our eyes ever vigilant on the new government."
Asked if he thought the protests were an appropriate response to the outcome of Tuesday's election, he replied: "Yes, absolutely. Things aren't being done right."
Demonstrators took to the streets in Miami, Los Angeles, New York and other US cities for a third straight night on Friday.
People gathered in New York's Washington Square neighborhood in lower Manhattan, some carrying enormous red balloons and placards with hearts and the words "peace and love."
Others held signs reading "Your Wall Can't Stand in Our Way" -- a reference to the anti-immigration barrier the billionaire real estate baron has promised to build on the US border with Mexico.
Earlier in the day a town in southern Italy where De Niro's grandparents came from offered the actor a means of escape.
"If after the disappointment of Trump, he wants to take refuge here, we are ready to welcome him," said Antonio Cerio, the mayor of Ferrazzano.
De Niro hasn't minced his words in his criticism of Trump, describing him as "a punk," "a pig" and "an idiot."
"I'd like to punch him in the face," he said before the election.
But the double Oscar-winning New Yorker said on ABC a day after Trump's victory: "I can't do that now, he's the president. And I have to respect that position."
"The Comedian," De Niro's passion project which took him eight years to bring to the big screen, was part of this year's program for the American Film Institute's annual AFI Fest in Los Angeles.
Its general release in the United States is on January 13.
The festival, which runs until Thursday next week, shows many of the films considered frontrunners for Oscars glory.
