The 'By the Sea' actress is said to be in early talks with 20th Century Fox about appearing in the adaptation of Agatha Christie's novel, which is being directed Sir Kenneth Branagh, who will also produce play the lead character, detective Hercule Poirot.
It is as-yet unknown who Angelina would play in the mystery.
'Blade Runner Two's' scriptwriter Michael Green is penning the screenplay for the movie.
The 1934 story revolves around a killing on the famous train.
It is up to Belgian detective Poirot to solve the case, with a number of passengers in the frame as the murderer.
It was previously claimed the movie will be a remake of Sidney Lumet's 1974 film, which starred Albert Finney as Poirot, who was investigating the murder of an American tycoon. Those playing the suspects included Lauren Bacall, Ingrid Bergman - who picked up a Best Supporting Actress Oscar - Jacqueline Bisset, Colin Blakely, Sean Connery, John Gielgud, Anthony Perkins, Vanessa Redgrave and Michael York.
The popular story was also depicted in a 2001 TV show which starred Alfred Molina and Leslie Caron.
Angelina's most recent film role was in 2015 drama 'By the Sea', which she also directed, opposite husband Brad Pitt.
She has spent more time behind the camera in recent years, with her directorial offerings including 'Unbroken' and 'In the Land of Blood and Honey'.
Meanwhile, Kenneth made his name with a series of Shakespeare adaptations, but he has recently made a move towards more populist material, having also helmed Marvel's 'Thor' and 'Jack Ryan: Shadow Recruit'.
He also revealed earlier this year that he is "very hopeful" Martin Scorsese will direct a movie adaptation of his 2013 'Macbeth' stage production.
The duo were said to have staged informal discussions about the idea and Sir Kenneth confirmed it was close to a reality.
He shared: "We're practically there... We will remount the production and all things being well Mr Scorsese will direct a film version of that production.
"Fingers are hovering above pieces of paper. Everybody wants to do it, it's just a question of schedules. I'm very, very, very, very hopeful it's going to happen."
