Herbal remedies are becoming increasingly popular for the treatment of depression. Recently, accumulating evidences reveal a positive effect of saffron (Crocus sativus L.) in relieving depressive symptoms. The objective of this meta-analysis was to assess the safety and efficacy of saffron in treating mild to moderate depression by synthesizing all available data.Relevant studies were retrieved from electronic databases and cross-checking of reference lists. Eligible trials were carefully reviewed, and necessary data were extracted. The Hamilton Rating Scale for Depression or Beck Depression Inventory scores, response rate, remission rate, and adverse effects were compared between saffron and placebo or saffron and antidepressants to assess the efficacy of saffron for depression.Twelve studies were included in the meta-analysis. Overall results showed that saffron possessed better efficacy in the improvement of depressive symptoms when compared with placebo, whereas saffron was as effective as synthetic antidepressants. No significant difference was detected in the incidence of adverse effects between saffron and placebo or between saffron and antidepressants.Saffron could be considered as an alternative to synthetic antidepressants in the treatment of mild to moderate depression. However, multicenter trials with larger sample size, longer treatment duration, and different ethnic groups are required to verify our results.