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A systematic review and a meta-analytic approach were considered to investigate the effects of lemon balm as a medicinal herb on anxiety and depression in clinical trials and its side effects. All randomized clinical trials published up to October 30, 2020 that examined lemon balm in patients with symptoms of depression or anxiety, with acute or chronic manifestations, were searched in 12 online databases. Statistical analysis was performed using RevMan software. Continuous data were analyzed using standardized mean differences. Statistical heterogeneity was assessed using Chi2, I2, and p value tests. Based on meta-analysis results, lemon balm significantly improved mean anxiety and depression scores compared with the placebo (SMD: -0.98; 95% CI: −1.63 to −0.33; p = 0.003), (SMD: -0.47; 95% CI: −0.73 to −0.21; p = 0.0005) respectively, without serious side effects. Current evidence suggests that lemon balm may be effective in improving anxiety and depressive symptoms, particularly in the acute setting. Due to the high level of heterogeneity between studies, results should be interpreted with caution. The small number of clinical trials and differences between their methods were the limitations of the present study. Further high-quality studies are needed to firmly establish the clinical efficacy of the lemon balm.