In an interview with Stephen Colbert, Harrison Ford explained how the filmmakers digitally de-aged him for the flashback sequence: "They have this artificial intelligence program that can go through every foot of film that Lucasfilm owns. Because I did a bunch of movies for them, they have all this footage, including film that wasn't printed. So they can mine it from where the light is coming from, from the expression. I don't know how they do it. But that's my actual face. Then I put little dots on my face and I say the words and they make [it]. It's fantastic." At 80, he is the oldest actor to be de-aged in a movie, surpassing Al Pacino, who was 79 when he was de-aged in The Irishman (2019).
John Rhys-Davies had expressed interest in reprising his role as Sallah from Les Aventuriers de l'arche perdue (1981) and Indiana Jones et la Dernière Croisade (1989). He was offered a cameo in the wedding scene in Indiana Jones et le Royaume du crâne de cristal (2008), but he "thought the character of Sallah is worth more to the audience than that."
Harrison Ford would embark on 40-mile bike rides and daily walks to get in shape for his Indiana Jones role.
George Lucas, Steven Spielberg and Paramount Pictures first agreed to five Indiana Jones films in 1979.
During the train sequence when Indy is looking for the Lance of Longinus inside the train car of artifacts, the Holy Hand Grenade of Antioch from Monty Python : Sacré Graal ! (1975) can be spotted on a shelf.
Anthony Ingruber: Voice actor and Harrison Ford lookalike, as a Dutch Prince bidding at the auction in Morocco. Ingruber played a young version of Ford's character in Adaline (2015).
Sean Connery: A couple of photos of Henry Jones Sr. can be seen in the apartment of Indiana Jones in New York.