The Sandman presents a rich tapestry of LGBTQ+ characters, including a non-binary Endless (Desire), a bisexual protagonist (Johanna Constantine), and a dignified drag queen (Hal). These characters are depicted with complexity, agency, and respect, with their identities normalized and celebrated within the narrative, contributing to a strong positive net impact.

The Sandman features multiple gender-diverse characters, including a trans woman (Hazel), a non-binary entity (Desire), and a gender-nonconforming drag queen (Hal). Their portrayals are consistently dignified, complex, and integral to the narrative, without their identities being sources of ridicule or misery. The show affirms the worth of these characters' lives and identities.

The Sandman features several characters, including Lucifer Morningstar and Lucienne, who were established as male in the original comic series but are portrayed as female in the show. The contemporary Constantine role, originally male, is also portrayed by a female character.

The show features multiple characters, including Death, Lucien, Rose Walker, Jed Walker, Cain, and Abel, who were depicted as white in the original comic book series but are portrayed by actors of different races in the adaptation.