Abstract： Objective： To observe the clinical effect of Chaihu Longgu Muli Decoction combined with agomelatine in females with depression complicated with sleep disorders. Methods ： A total of 120 cases of patients with depression complicated with sleep disorders were divided into the observation group and the control group according to the randomized principle，with 60 cases in each group. The control group was treated with Agomelatine， and the observation group was additionally treated with Chaihu Longgu Muli Decoction based on the treatment of the control group. After 8-week treatment，the situation of scales in depression and sleep，the levels of neurotransmitters and hormones，the clinical effects，and the incidence of adverse reactions were compared between the two groups. Results： The total effective rate was 93.33% in the observation group and 80.00% in the control group，the difference being significant (P＜0.05). After treatment for 4 and 8 weeks respectively， the scores of Hamilton Depression Scale (HAMD) and Pittsburgh Sleep Quality Index (PSQI) in the two groups were decreased when compared with those before treatment，and the scores of HAMD and PSQI in the observation group were lower than those in the control group，differences being significant (P＜0.05). After 8-week treatment，the levels of 5- hydroxytryptamine (5- HT) and norepinephrine (NE) in the two groups were increased when compared with those before treatment， and the levels of 5- HT and NE in the observation group were higher than those in the control group， differences being significant (P＜0.05)； the levels of follicle- stimulating hormone (FSH) in the two groups were decreased when compared with those before treatment，and the FSH level in the observation group was lower than that in the control group，the difference being significant (P＜0.05). The incidence of adverse reactions was 28.33% in the observation group and 23.33% in the control group， there being no significance in the difference (P＞0.05). Conclusion： Chaihu Longgu Muli Decoction combined with western medicine has a significant clinical effect in females with depression complicated with sleep disorders，which can further enhance the improvement effect of the symptom of depression with good safety.