Objective: This study examined associations of discrimination, social support, and their interaction, with internalizing symptoms among Asian-Pacific Islander (API) sexual and gender minority (SGM) adults in the U.S. Method: Analyses included data from 544 participants who completed an online survey, including measures of three internalizing symptoms (anxiety, depression, and somatization), five forms of discrimination (racism, heterosexism/cisgenderism, and three forms of intersectional discrimination), and two types of social support (acceptance for sexual/gender identity, general social support). Results: All forms of discrimination were positively associated with all internalizing symptoms, with the strongest associations with somatization symptoms; further, acceptance for sexual/gender identity was negatively associated with all internalizing symptoms. Overall social support did not buffer associations of discrimination with internalizing symptoms. Positive associations between discrimination and symptoms were generally stronger at higher social support levels, and social support had weaker negative associations with internalizing symptoms at higher discrimination levels. Conclusion: Findings suggest the importance of increasing sexual/gender identity-specific social support, attending to somatization symptoms as an important manifestation of discrimination and reducing societal discrimination to address mental health needs of API SGM adults in the U.S. Public Significance StatementThe results of this study suggest detrimental mental health consequences of multiple forms of discrimination faced by Asian-Pacific Islander sexual and gender minority adults in the U.S. Results also support that there are unique mental health benefits associated with social support specific to sexual/ gender identity and that it is important to examine physiological symptoms as a potential manifestation of discrimination experiences.