Stigma is known to have major impacts on the physical and psychological health of many groups. Psychological inflexibility is a psychological process that may help explain the impact of stigma on both self and others. Accordingly, acceptance and commitment therapy (ACT), which targets psychological inflexibility, has been researched as a potential treatment for stigma. In order to provide a comprehensive overview of these issues, this paper offers a systematic review and meta-analysis of the association between psychological inflexibility and stigma, as well as a systematic review of ACT interventions for stigma. The results of the meta-analysis showed a positive, medium-to-large association between psychological inflexibility and stigma measures aggregating across 16 studies. The systematic review of interventions identified 15 studies on ACT interventions for stigma. Initial findings indicate consistent reductions in stigma following ACT interventions, as well as improved outcomes relative to active controls. Data on mediation and moderation, as well as long-term outcomes, are also presented. Implications for conceptualizing and treating stigma, and limitations of the research, are discussed.