Brothers & Sisters features a prominent gay character, Kevin Walker, whose relationship and family life are depicted with dignity and complexity. The narrative normalizes LGBTQ+ relationships and families, portraying their challenges as universal human experiences rather than as a consequence of their identity, resulting in a largely affirming portrayal.

The series portrays Christianity primarily through cultural traditions (weddings, funerals) and as a source of comfort or moral guidance for characters during personal crises. While not a central theme, its presence is treated with respect and sympathy, never depicted as oppressive or hypocritical.

The series respectfully portrays Judaism through the character of Scotty Wandell and his family, integrating Jewish traditions and heritage into the broader family narrative. The depiction is consistently positive, emphasizing acceptance and the richness of cultural diversity without critique or negative stereotypes.