Background <p>Although previous research has delved into the realm of mindfulness, uncovering numerous significant insights, this study introduces a fresh perspective by linking mindfulness with depression, suppression, and self-esteem—a connection that has not been extensively explored. Considering the cognitive focus of mindfulness and the cognitive vulnerabilities associated with depression, we proposed and examined the mediating effects of suppression and self-esteem between mindfulness and depression.</p> Methods <p>A sample of 607 participants (age = 22.00 ± 2.63 years, 62.1% female) completed a questionnaire regarding mindfulness, thought suppression, emotion suppression, self-esteem, and depression. Data were analyzed using linear regression and structural equation modeling (SEM).</p> Results <p>(1) The total effect of mindfulness on depression was − 0.642. The direct mediating effects of self-esteem and thought suppression were − 0.407 and − 0.086, respectively. The chain mediating effects of emotion suppression and thought suppression, as well as emotion suppression and self-esteem, were − 0.035 and − 0.037, respectively. However, the direct effect of mindfulness on depression was not statistically significant (<i>p</i> = 0.174). (2) Among the five facets of mindfulness, acting with awareness, non-judgment, and describing had the strongest predictive effect for self-esteem, thought suppression, and emotion suppression, respectively.</p> Conclusions <p>Thought suppression and self-esteem mediate mindfulness’s impact on depression directly, while emotion suppression only plays a role through chain mediations. Different mindfulness facets have varied effects. These findings offer valuable insights for depression intervention and prevention.</p>