Abstract：Objective：To observe the efficacy of Jieyu Mixture combined with Flupentixol and Melitracen Tablets in the treatment of depression and its effect on bile acid levels. Methods： A total of 90 patients with depression admitted to Ningbo Zhenhai Hospital of Traditional Chinese Medicine from August 2023 to August 2024 were selected and randomly divided into the treatment group and the control group using the random number table method， with 45 cases in each group. During the treatment，5 cases dropped out，finally 42 cases in the treatment group and 43 cases in the control group enrolled. The control group was treated with Flupentixol and Melitracen Tablets，while the treatment group was treated with Jieyu Mixture on the basis of the control group's regimen. The clinical efficacy and incidence of adverse reactions were compared between the two groups. Changes in Hamilton Depression Rating Scale （HAMD） scores， traditional Chinese medicine syndrome scores， and serum total bile acid （TBA） levels before and after treatment were compared between the two groups. Results：The total clinical effective rate was 88.10% （37/42） in the treatment group and 69.77% （30/43） in the control group，and the difference between the two groups was statistically significant （P＜0.05）. After treatment， the scores for diurnal variation factor， retardation factor， sleep disturbance factor， hopelessness factor， and the total HAMD score in the treatment group were lower than those in the control group（ P＜0.05）. After treatment，there were no statistically significant differences between the two groups in scores for anxiety/somatization factor， weight factor， and cognitive disturbance factor （P＞0.05）. After treatment， traditional Chinese medicine syndrome scores in both groups decreased compared with those before treatment （P＜0.05），and the traditional Chinese medicine syndrome score in the treatment group was lower than that in the control group （P＜0.05）. After treatment，bile acid levels in both groups decreased compared with those before treatment （P＜0.05），and the bile acid level in the treatment group was lower than that in the control group （P＜0.05）. The incidence of adverse reactions was 4.8% in the treatment group and 13.95% in the control group， and there was no statistically significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. Conclusion： Jieyu Mixture combined with Flupentixol and Melitracen Tablets demonstrates good efficacy in the treatment of depression，which can reduce serum bile acid levels，relieve symptoms and has a high safety profile.