The movie mogul was in the audience at a showcase for emerging talent when comedian Kelly Bachman criticised him on stage.
Weinstein has been accused of several counts of sexual assault, which he denies.
Bachman referred to him as "the elephant in the room" and "Freddy Krueger" as she spoke at the event.
His representative said the behaviour of the women was "rude" and "uncalled for".
"I didn't know we had to bring our own Mace and rape whistles to Actor's Hour," Bachman is seen saying in video footage posted on Instagram.
She was booed and told to be quiet by members of the audience, to which she replied: "Sorry, that killed at group therapy for rape survivors."
However, some members of the audience then cheered and applauded her.
After the event, Bachman told the Guardian she "felt like the air was sucked out of the room" when she spoke about Weinstein on stage.
Fellow comedian Amber Rollo and actress Zoe Stuckles reportedly approached Weinstein's table at the interval of the event in the city's Lower East Side.
"Nobody's gonna say anything?" Stuckles shouted in the direction of the filmmaker - who was sitting with two bodyguards - before both she and Rollo were asked to leave.
Footage of the exchange was later posted on Facebook and reproduced by The Guardian.