"I behaved in a way, and I allowed others to behave in a way that was really unprofessional, and I'm sorry," he told the Associated Press.
The Oscar winner was sued by two female crew members who accused him of sexual harassment while working on the mockumentary film, which he directed.
Affleck denied the allegations and the lawsuits were settled out of court.
Affleck settles harassment claim
"That I was ever involved in a conflict that resulted in a lawsuit is something that I really regret," he said.
"I had never had any complaints like that made about me before in my life and it was really embarrassing, and I didn't know how to handle it, and I didn't agree with everything, the way I was being described and the things that were said about me," Affleck said.
"But I wanted to try to make it right, and so we made it right in the way that was asked at the time."
'The buck stops with me'
Affleck was also a producer on I'm Still Here, in which actor Joaquin Phoenix was seen pretending to launch a musical alter-ego.
He said that meant "the buck had to stop" with him and that he had "to accept responsibility" for what took place on the set.
Affleck's accusers, producer Amanda White and director of photography Magdalena Gorka, alleged that they were repeatedly subjected to sexual innuendoes and unwanted advances.
"It was an unprofessional environment," Affleck said. "And I contributed to that unprofessional environment and I tolerated that kind of behaviour from other people and I wish that I hadn't, and I regret a lot of that."
Affleck, the younger brother of Hollywood star Ben, also said that turning down a presenting role at this year's Oscars had been "the right thing to do".
Having won the best actor award in 2017 for Manchester by the Sea, the 42-year-old had been expected to appear at this year's ceremony to present the best actress prize.
Following his withdrawal, the statuette was instead presented to Frances McDormand by Jennifer Lawrence and Jodie Foster.
"Given everything that was going on in our culture at the moment... having two incredible women go present the best actress award felt like the right thing," he told AP's Lindsey Bahr.
Affleck pulls out of 2018 Oscars
In his first extensive interview since pulling out of this year's Oscars, Affleck addressed the concerns of the #MeToo movement and said he "needed to keep his mouth shut and listen".
"Women have been underrepresented and underpaid and objectified and diminished and humiliated and belittled in a bazillion ways," he said.
"No-one was really making too much of a fuss about it, myself included, until [there were] a few women with the kind of courage and wisdom to stand up and say, 'You know what? Enough is enough.'"
Affleck will next be seen in cinemas in The Old Man and the Gun with Robert Redford. Redford said this week that it would be his final film as an actor.