Ryan Reynolds has said of being slapped around in this movie: "In Hitman's Wife's Bodyguard, I'm slapped in the face twice by Salma Hayek and once by Samuel L. Jackson. For the record, it was Salma who didn't pull the punches. Not even once. I can still feel the sharp sting of her tiny hand working its way into my soft Hollywood cheekbones. May God have mercy on her soul."
Jonny James and Venice Smith, the actors who, respectively, portray Johan and Gary, the characters that act as short lived decoys for Ryan Reynolds's and Samuel L. Jackson's characters, are actually their stunt doubles.
The mug shot of Michael Bryce in an ugly Christmas sweater was actually from Ryan Reynolds's real-life Instagram from 2018. Hugh Jackman and Jake Gyllenhaal pranked Reynolds to an ugly Christmas sweater party that wasn't really an ugly Christmas sweater party. The photo is a cropped version without Jackman and Gyllenhaal and has since become a popular meme template.
Salma Hayek refused to do the shot where all three main characters are drugged and fall on each other, when she found out that Ryan Reynolds' face would end up on her butt, and her face would be against Samuel L. Jackson's crotch. They had to use a body double for her.
The possibility of another sequel has been touted by the film's director Patrick Hughes prior to the picture's premiere in June 2021. He said of another sequel in an interview: "It dawned on me during the first film that the endlessly suffering fool who is Michael Bryce, must suffer endlessly, therefore we must endlessly make sequels. As a result, the sequel does leave things ready for another film. All we can say is that it sets Ryan up to suffer. Endlessly."