摘要:Background: Depression represents a serious public health concern, imposing a high burden, both in epidemiological and clinical terms. Crocus sativus (Saffron) is a herbal remedy that has anti-cancer, anti-oxidant, anti-inflammatory and anti-platelet properties. However, the exact mechanisms of Saffron in treating depression are not yet clear. This study was conducted to evaluate the effectiveness of Saffron versus placebo and Fluoxetine in the treatment of depressed patients. Methods: Different bibliographic thesauri, namely the Cochrane Library, Scopus, PubMed/MEDLINE, Centre for Reviews and Dissemination (CRD), EMBASE, and ISI/Web of Science (WoS) were searched up to May 2018. Effect sizes were computed as Standardized Mean Differences (SMD) with their 95% confidence interval (CI). To evaluate the heterogeneity among the studies, I2, test was carried out. Results: Eight studies were included. The SMD was −0.86 (95% CI: −1.73 to 0.00) concerning the comparison of Saffron with placebo. The SMD was found to be 0.11 (95% CI: −0.20 to 0.43) concerning the comparison of Saffron with Fluoxetine. In both sensitivity analyses, the results did not statistically change, confirming the stability of the findings. Conclusion: The findings of this study showed that Saffron administration was well comparable with Fluoxetine and placebo.