Blindspot features Tasha Zapata, a main character whose bisexuality/lesbianism is explored through a respectful and complex relationship with Briana. Her queer identity is depicted with dignity and agency, integrated naturally into her character arc without being a source of mockery or negative stereotypes, contributing to an overall affirming portrayal.

Blindspot includes Boston Arliss Crab, a transgender man, as a recurring supporting character. His identity is acknowledged factually, particularly in relation to his past with Rich Dotcom, but it is not central to his character's arc or the show's primary themes. The portrayal is incidental, neither uplifting nor denigrating, treating his identity as a personal detail rather than a narrative focus.

The show features multiple female characters, most notably Jane Doe and Tasha Zapata, who consistently engage in and win close-quarters physical combat against one or more male opponents, utilizing martial arts and hand-to-hand techniques.

The series frequently depicts antagonists who are Islamic extremists, but the narrative consistently frames their actions as a radical perversion of the faith, not representative of Islam itself. The show often includes Muslim characters who are allies or victims, thereby distinguishing between extremist ideologies and the broader religion, positioning the audience to condemn bigotry and misuse of faith.