She is the older sister of Jake Gyllenhaal and the daughter of director Stephen Gyllenhaal and screenwriter Naomi Foner. Gyllenhaal began her acting career in a film directed by her father, and later achieved recognition in her own right playing her real-life brother's on-screen sister in the cult hit Donnie Darko. Gyllenhaal made her breakthrough in the sadomasochistic romance, Secretary, for which she received a Golden Globe nomination.
Gyllenhaal has chosen an eclectic range of roles, from indie films such as Sherrybaby, for which she was also nominated for a Golden Globe, to the romantic comedy Trust the Man and big-budget studio films such as World Trade Center and The Dark Knight.