Objectives: Previous studies revealed a positive association between neuroticism and depression. This study further extended the previous findings by exploring the psychological processes underlying this association among Chinese postgraduates. Guided by theoretical models and empirical research, we proposed a multiple mediation and moderated mediation model to investigate the roles of dispositional mindfulness and cognitive reappraisal in the relationship between neuroticism and depression.Methods: Using the NEO Five-Factor Inventory, Beck Depression Inventory, Mindfulness Attention Awareness Scale, and Emotion Regulation Questionnaire, 1103 first-year postgraduates at a comprehensive university in China were surveyed. Path analysis was adopted to test the models.Results: The results showed that dispositional mindfulness mediated the association between neuroticism and depression. Further, this mediating effect was moderated by cognitive reappraisal, with this effect being stronger in individuals with low engagement in cognitive reappraisal.Conclusion: The results support interrelations among neuroticism, depression, dispositional mindfulness, and cognitive reappraisal as moderated mediation rather than multiple mediation. The results enhance our understanding of psychological mechanisms between neuroticism and depression and provide suggestions for interventions to prevent or reduce depression in highly neurotic postgraduates.