Numerous adverse effects of antidepressants as well as the attitudes of breastfeeding mothers, who prefer to consume herbal medicine rather than chemical drugs, encouraged us to assess the effects of saffron (Crocus sativus L.) on mothers suffering from mild-to-moderate postpartum depressive disorder.A double-blind, randomized, and placebo-controlled trial was conducted on 60 new mothers who had a maximum score of 29 on the Beck Depression Inventory-Second Edition (BDI-II). They were randomly assigned to the saffron (15 mg/Bid) or placebo group. The primary outcome was a change in the BDI-II scores 8 weeks after treatment compared to the baseline. The response and remission rates were considered to be secondary outcome measures.Saffron had a more significant impact on the BDI-II scores than the placebo. The mean BDI-II scores decreased from 20.3 ± 5.7 to 8.4 ± 3.7 for the saffron group (p < .0001) and from 19.8 ± 3.2 to 15.1 ± 5.4 for the placebo group (p < .01). In the final assessment, 96% of the saffron group were in remission compared to 43% of the placebo group (p < .01). The complete response rates were 6% for the placebo group and 66% for the saffron group.When administered to treat minor PPD in breastfeeding mothers, saffron had a more significant impact on the BDI-II than the placebo.