To investigate the clinical efficacy, adverse reaction and safety of Jieyu pill (JYP) in treating depression. The randomized controlled trial was conducted in 28 patients in the treated group and 29 patients in the control group treated with maprotiline (Map). The efficacy of treatment was evaluated before treatment and 14, 28 and 42 days after treatment, with Hamilton depression rating scale (HAMD), self-rating scale for depression (SDS), self-rating scale for anxiety (SAS) and clinical global impression (CGI), the adverse reaction was assessed by Asberg Rating Scale (ARS). JYP was effective in treating depression, the markedly effective rate being 78.8%, corresponded to that of Map (82.8%, P > 0.05). After treatment, the scores assessed by HAMD, SDS and SAS were all lower than those before treatment (P < 0.01) respectively, but comparison between the two groups showed insignificant difference (P > 0.05). However, scores of ARS were significantly lower in the treated group than that in the control group, and the efficacy index of JYP was significantly higher than that of Map (P < 0.01). JYP in treating depression shows the efficacy corresponded to that of Map and with less adverse reaction.