House includes LGBTQ+ characters, most notably Dr. Remy "Thirteen" Hadley, whose bisexuality is presented matter-of-factly. Numerous patient storylines also feature LGBTQ+ individuals, with their identities typically being incidental to the medical plots. While some episodes explore complex or challenging situations, the show generally avoids strong positive or negative arcs, treating these identities as a normal part of human diversity without significant uplift or denigration.

House features transsexual and intersex characters, notably a trans woman in S7E14. While Dr. House makes initial insensitive remarks, the show's narrative and other characters actively challenge this, portraying the patient with dignity and agency. Intersex characters are also handled with medical respect, contributing to a net positive portrayal where identity is not a source of ridicule or villainy.

The show consistently questions traditional family norms, frequently depicting marriage as fraught with infidelity and divorce, parental authority as flawed or deceptive, and religion in family life as a source of conflict. It normalizes non-traditional relationships and often highlights the dysfunction within conventional family units.

The show frequently portrays Christian beliefs, particularly when they conflict with scientific reasoning or medical necessity, as irrational or problematic. Through the protagonist's cynical lens, and often validated by narrative outcomes, faith is depicted as a hindrance to objective truth and effective treatment.