This mixed-methods study examined how WiseGuyz, a gender-transformative healthy relationships program, can support positive sexual health self-efficacy (SHSE) among adolescents. 570 adolescent boys provided data on SHSE from before to after the program, and 20 adolescent boys participated in interviews and focus groups to discuss their sexual health education needs. Results showed that boys who participated in WiseGuyz reported a significant increase in SHSE from pretest to post-test and that WiseGuyz was different from typical school-based sexual health education in terms of content and facilitation and increasing program engagement. These findings indicate the potential for gender-transformative interventions in supporting positive SHSE.