Sense8 features multiple central LGBTQ+ characters, including a transgender woman and a gay man, whose identities and relationships are portrayed with dignity, complexity, and agency. The narrative consistently affirms LGBTQ+ lives and love, framing prejudice as an external force to be overcome by supportive chosen families.

Sense8 features Nomi Marks, a trans woman, as a central, complex, and highly capable protagonist. Her trans identity is portrayed with dignity and agency, supported by a loving relationship and a narrative that frames her struggles as external prejudice rather than internal conflict. The show consistently affirms the worth and strength of her trans life.

The series portrays Christianity with nuance, showing both the bigotry of Nomi's mother, which the narrative condemns, and the genuine, positive faith of Capheus, which serves as a source of strength and community. The film's message affirms the virtues of faith while critiquing its misuse for prejudice.

Hinduism is depicted positively through Kala Dandekar, whose faith is a central part of her identity, providing moral guidance, comfort, and a strong sense of community and tradition. While she grapples with reconciling her beliefs with new realities, the rituals and cultural aspects are shown with respect and beauty.