OBJECTIVE: Stress and burnout are serious problems that impair the well-being and academic performance of medical students. Published systematic reviews and meta-analyses on interventions to reduce the stress experienced by medical students did not conclude which interventions are the most effective due to the heterogeneity of the studies. To enhance the hierarchy of evidence, our study selected only randomized controlled studies. The aims were to obtain more reliable outcomes and to precisely summarize the specific interventions which effectively reduce the stress levels and burnout of medical students. METHODS: We performed a systematic review and meta-analysis according to PRISMA guidelines. Medical databases (Embase, Ovid, and CINAHL) were searched for relevant randomized controlled studies published up to December 2019. Two treatment timepoints (postintervention, and the 6-month follow-up) were chosen. Stress measure outcomes were the main outcomes. A random effects model was used. An intention-to-treat analysis was conducted. RESULTS: Six high-quality studies were found. They compared the efficacies of mindfulness-based interventions and clerkship as usual (N = 689). The stress measurement scores of each mindfulness-based intervention at postintervention were significantly better than those of the control groups, with medium effect size and low heterogeneity (95% CI 0.07-0.51; p = 0.01; I-squared index = 45%). At the 6-month follow-up, the mindfulness groups had significantly better results than the control groups, with medium effect size and negligible heterogeneity (95% CI 0.06-0.55; p = 0.02; I-squared index = 0%). DISCUSSION: The results indicate that mindfulness-based interventions are effective in reducing subjective stress in medical students at both the short- and long-term intervention timepoints.