Sexual minority (e.g. lesbian, gay, bisexual, questioning; LGBQ) and gender minority (e.g. transgender) youth experience myriad health risks. Gay-Straight Alliances (GSAs) are school-based settings where they may have opportunities to discuss substance use, mental health, and sexual health issues in ways that are safe and tailored to their experiences. Attention to these topics in GSAs could aid in developing programming for these settings. Among 295 youth from 33 Massachusetts high-school GSAs (69% LGBQ, 68% cisgender female, 68% White, Mage = 16.06), we examined how often youth discussed these topics within their GSA and identified factors associated with having more of these discussions. Youth and GSAs as a whole varied in their frequency of discussing these topics. Youth who accessed more information/resources in the GSA and did more advocacy more frequently engaged in discussions around substance use, mental health and sexual health. Youth who reported greater victimization more often discussed substance use and mental health, but not sexual health. Finally, GSAs whose members collectively reported greater victimization more frequently discussed these topics. These findings can assist the development of health programming to be delivered within GSAs.