Guile's family consist of his wife Julia and their daughter Amy. They first appeared in Guile's ending from Street Fighter II, urging Guile not to kill M. Bison as it would make him a murderer and would not bring Charlie back. They also appear in Guile's ending from Street Fighter IV, Capcom Fighting Evolution and SNK vs. Capcom: SVC Chaos.
Julia deeply loves Guile and she seeks that he do the right thing with determination. However, she is also very understanding, and allows Guile to find Charlie, because she hopes that with this he will recover from his negative feelings, despite the pain this causes her.
Amy, known as Chris (クリス Kurisu?) in Japan, is the only daughter of Guile and Julia. She is also the niece of Eliza, cousin of Mel, and a penpal of Dhalsim's son Datta. Amy is a gentle girl that doesn't like martial arts and is always worried with her father due to his job. She exchanges mails on her phone, but continues corresponding with Datta with letters. She likes to play with her cousin Mel and to help others. Every day she takes her dog Sabu to a walk.
- Gunloc's profile in Saturday Night Slam Masters indirectly mentions the possibility of him being related to Guile. The arcade version of Street Fighter: The Movie states that Blade (actually Gunloc in disguise) is Guile's brother, but the game is not considered part of the main Street Fighter continuity, and Blade's Shadaloo C.R.I. entry does not mention Guile.