Ugly Betty offers a largely positive portrayal of LGBTQ+ characters. Through the nuanced arcs of Marc St. James and Justin Suarez, the show depicts their journeys of self-discovery, coming out, and finding love with dignity, complexity, and strong familial and social support, affirming the worth of queer lives.

"Ugly Betty" features Alexis Meade, a prominent transsexual character whose journey from secret transition to open acceptance by her family forms a significant plotline. The show portrays her with complexity and agency, framing the family's initial struggles with acceptance as their own challenge. Ultimately, the narrative affirms her identity and worth, contributing to a net positive portrayal.

The American adaptation "Ugly Betty" features several characters, such as Daniel Meade, Amanda Tanen, and Wilhelmina Slater, who were originally portrayed as Latino/Latina in the Colombian source material "Yo soy Betty, la fea." These characters are depicted by white or Black actors in the US series, constituting multiple instances of race swapping.

The show portrays the Suarez family's Catholic faith as a foundational element of their identity, providing strong family values, community support, and moral guidance. Despite comedic situations involving character interpretations, the narrative consistently treats Catholicism with respect, affirming its positive influence.