Despite the well-documented association between experiences of substance use stigma and adverse mental health outcomes, little is known about the mechanisms underlying this association. Utilizing a community sample of substance-using adults who have experienced at least one traumatic event in their lifetime, the current study examined the role of dysregulation stemming from both negative and positive emotions in the relation between substance use stigma and depressive symptoms. Community participants (N = 320, 46.9% women) completed self-report measures of substance-use-related stigma experiences, negative and positive emotion dysregulation, and depressive symptoms. Results showed that, adjusting for gender and substance use severity, substance use stigma was positively associated with emotion dysregulation, which in turn related to depressive symptoms. Substance use stigma was also found to be indirectly associated with depressive symptoms through emotion dysregulation, suggesting that emotion dysregulation accounted for the significant association between substance use stigma and depressive symptoms. These findings provide initial support for the role of emotion dysregulation as a mechanism through which stigma operates to undermine the mental health of substance-using, trauma-exposed individuals. Results underscore the potential utility of targeting emotion dysregulation in intervention efforts that are designed to facilitate stigma coping among individuals who use alcohol and/or drugs.