Orphan Black features prominent and positively portrayed LGBTQ+ characters, including a lead lesbian clone, Cosima, whose relationship with Delphine is central and affirming, and a key gay supporting character, Felix. The show depicts their identities with dignity and complexity, framing obstacles as external to their queer identities, thus contributing to a supportive and validating overall portrayal.

Orphan Black features Tony Sawicki, a trans man clone, who is portrayed with dignity and agency. His trans identity is accepted by other characters and is not a source of ridicule or primary conflict. The show integrates him respectfully into the overarching narrative, focusing on his role as a clone rather than his gender identity as a source of struggle.

The show portrays the Proletheans, a fundamentalist Christian sect, as a dangerous and violent antagonist group. Their religious beliefs are used to justify horrific acts, including forced impregnation and murder, with the narrative clearly condemning their extremism and cruelty.