Portman won best actress for Jackie, in which she portrays Jacqueline Kennedy after John F Kennedy`s assassination.
The event styles itself as the start of the awards season, but is regarded with scepticism by some industry observers.
Winners were announced in advance with no nominations. Many of the winning films have not yet been released and an anonymous panel chooses the recipients.
Natalie Portman is pregnant with her second child
But that did not stop an A-list crowd turning up to the ceremony, which was compered by TV host James Corden - although he did joke at one point that they were "fake awards".
The night was also peppered with references to Tuesday`s US presidential election.
"Tonight is actually rigged," Corden told the audience at the Beverly Hilton Hotel, referring to Donald Trump`s complaints about the election. "Literally, none of this is real."
He also joked that it was "the last awards show before the apocalypse".
Tom Hanks received his trophy from Sully director Clint Eastwood
Nicole Kidman was joined by her Lion co-star Dev Patel
Robert De Niro, who won the comedy award for the film The Comedian, compared Mr Trump to the "totally insane" General Jack D Ripper from Stanley Kubrick`s Dr Strangelove.
He said: "It`s two days until a frightening election. The shadow of politics is hanging over us whether we like it or not.
"It`s hard for me to think about anything else so let me lay it out right here. We have the opportunity to prevent a comedy from turning into a tragedy. Vote for Hillary Tuesday."
Tom Hanks won the best actor award for the film Sully, in which he played Captain Chesley Sullenberger, the pilot who safely landed a passenger plane on New York`s Hudson River in 2009.
Hugh Grant was reunited with his Four Weddings and a Funeral co-star Andie MacDowell
Lily Collins (left) and Naomie Harris also received prizes
Nicole Kidman won the supporting actress award for Lion, while Hugh Grant was named best supporting actor for his role in Florence Foster Jenkins.
He was presented with the award by Andie MacDowell, his co-star in the 1994 film Four Weddings And A Funeral.
Addressing her on stage, Grant said: "I`m just depressed at how much better preserved you are than I am after 22 years. Do you use any special creams or anything like that?
"It`s amazing. You`re still a southern peach and I am, according to Twitter, a scrotum.
"I almost never get a prize and I`m so pleased with this one. It will not be in my loo or used as a doorstep."
British actress Naomie Harris received the breakout actress award for her work in Moonlight, while Lily Collins, the daughter of singer Phil, was given the New Hollywood award for Rules Don`t Apply.
Awards season kicks off in earnest when the Golden Globe nominations are announced on 12 December, and will culminate with the Oscars on 27 February.
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