Type 2 diabetes patients often experience distress that adversely impacts their health-related quality of life (HRQoL). However, studies remain scarce on the pathways explaining the poor health outcomes. This study investigated the mediating link between diabetes distress (DD) and HRQoL through mindfulness and the moderating role of social support in this link. Utilizing a cross-sectional design, 276 type 2 diabetes patients completed measures of relevant variables. Results of moderated mediation analysis showed that social support moderated the mediating effect of mindfulness in the link between DD and HRQoL. Intervention may integrate mindfulness-based therapies with targeted support enhancements to improve patients’ health.