The celebrated actor is famed for his appearances in mobster-themed films, starring in classics such as "The Godfather Part II" and "Goodfellas" - and he sees a lot of similarities between his characters and the Potus.
"Today, we have a weird twisted president who thinks he's a gangster, who's not even a very good gangster," he shared on Friday's October 11 instalment of Britain's "The Graham Norton Show". "Gangsters have honour, you shake a hand and they have your word and you have theirs and that's it.
"But with this guy, it's not the case," the star lamented.
De Niro is a longtime critic of the 45th President, and recently labelled the businessman-turned-politician "medically crazy," adding: "He is worse than I ever could have imagined."
He went on to suggest the current political landscape may be part of the reason his movies still appeal to audiences but he insisted his characters differ because they "know right from wrong" - something that was also relevant from the '50s through the '70s during the time of the Vietnam War.
"(It) was more than we were seeing from our leaders, we were not being told the truth about what was really going on," he said, adding of the films' enduring appeal: "I guess it's because (gangsters) defy the law, yet have their own laws, structure and culture... There's more honour."
The actor stars as gangland enforcer Frank Sheeran in Netflix's "The Irishman", which will enjoy a limited run in theatres from November 1 before hitting the streaming service later that month.