Objective To evaluate the efficacy and clinical safety of berberine hydrochloride （BBR） adjunctive therapy for anxiety and insomnia in patients with depressive disorder. Methods From September 2022 to October 2023， 78 patients with depressive disorder in the outpatient or ward of the Zhumadian Second People's Hospital of Henan Province were selected as the research subject. Using a double-blind randomized placebo-controlled clinical trial method， the enrolled patients were randomly divided into a BBR group （n=39） and a placebo group （n=39） by a 1∶1 ratio， were given BBR and placebo， respectively， and were treated with a combination of selective serotonin reuptake inhibitors （SSRIs） for 8 weeks. At baseline and weeks 2， 4， 6， and 8， the patient's anxiety symptoms were evaluated using the Hamilton Anxiety Scale （HAMA）. Pittsburgh Sleep Quality Index （PSQI） was used to evaluate the sleep quality of patients at baseline and 4 and 8 weeks， and the Patient Assessment of Constipation Symptom （PAC-SYM） was used to evaluate the clinical safety of BBR. Repeated measures analysis of variance was used to compare the effects of inter group （BBR group and placebo group）， intra group （at various time points）， and interaction （group * time）. Covariance analysis and Wilcoxon rank sum test were used to explore the differences between two groups of patients at different time points relative to baseline. Binary Logistic regression was used to analyze the anxiety response rate and relief rate of two groups of patients. Kaplan-Meier survival curve was used to evaluate the time required for anxiety response and relief in two groups of patients. Results A total of 68 patients with depressive disorder were included， with 34 cases in BBR group and 34 cases in placebo group， and the dropout rates in both groups were 12.8%（5/39）. Repeated measures analysis of variance showed that compared with placebo group， the HAMA score of BBR group decreased at 6 and 8 weeks， and the difference was statistically significant （P ＜ 0.05）. Covariance analysis showed that there were statistically significant differences in HAMA score changes between BBR group and placebo group at 6 weeks ［（11.44±6.15） vs （6.53±8.50）， P＜ 0.001）］ and 8 weeks ［（11.29±5.94） vs （7.91±8.10）， P=0.005］. Logistic regression showed that the anxiety response rate of BBR group increased at 6 weeks ［OR=8.99， 95%CI （2.22， 36.44）， P=0.002］ and the relief rate increased at 8 weeks ［OR=3.45， 95%CI （1.00， 11.86）， P=0.049］. Survival analysis showed that there was no statistically significant difference in the time required for the response and relief to anxiety between the two groups of patients （all P＞ 0.05）. Repeated measures analysis of variance， covariance analysis， and Logistic regression analysis showed that there was no statistically significant difference in PSQI scores， sleep relief rates， and response rates at different time points between BBR group and placebo group at 4 weeks and 8 weeks （all P＞ 0.05）. Covariance analysis showed that there was no statistically significant difference in the changes in PAC-SYM scores relative to baseline scores between BBR group and placebo group at weeks 4 and 8 （P＞ 0.05）. Conclusions BBR adjunctive therapy may be an effective and safe method to improve anxiety symptoms in patients with depressive disorder.