Abstract： Objective： To observe the clinical efficacy of brain-gut co-treatment acupuncture combined with Zuogui Decoction plus Xiaoyao Powder in treating perimenopausal depression of kidney deficiency and liver stagnation type and its effects on gut microbiota. Methods： A total of 120 patients with perimenopausal depression of kidney deficiency and liver stagnation type treated at Zhenhai Hospital of Traditional Chinese Medicine from August 2022 to January 2024 were selected and divided into the acupuncture group and the acupuncture-medication group using the random number table method，with 60 cases in each group. Both groups received brain-gut co-treatment acupuncture therapy， while the acupuncture-medication group additionally received Zuogui Decoction plus Xiaoyao Powder. Both groups were treated continuously for four weeks. Clinical efficacy and safety were compared， along with modified Kupperman scores， Pittsburgh Sleep Quality Index（PSQI）scores， traditional Chinese medicine syndrome scores， levels of reproductive endocrine hormones [estradiol（E2），follicle-stimulating hormone（FSH），luteinizing hormone （LH）]， levels of neurotransmitters [serotonin（5-HT），norepinephrine（NE）]，and gut microbiota composition before and after treatment. Results： After treatment， the total effective rate was 86.67%（52 / 60） in the acupuncturemedication group， significantly higher than that of 66.67%（40/60）in the acupuncture group（P＜0.05）. Modified Kupperman scores， PSQI scores， and traditional Chinese medicine syndrome scores decreased in both groups compared to before treatment （P＜0.05）， with the acupuncture-medication group showing lower scores than the acupuncture group（P＜0.05）. After treatment， the FSH and LH levels decreased in both groups compared to before treatment（P＜0.05），with the acupuncture-medication group showing lower levels than the acupuncture group（P＜ 0.05）. After treatment， the E2 levels increased in both groups compared to before treatment（P＜0.05）， with the acupuncture-medication group showing higher levels than the acupuncture group（P＜0.05）. After treatment，the 5-HT and NE levels increased in both groups compared to before treatment（P＜0.05），with the acupuncture-medication group showing higher levels than the acupuncture group （P＜0.05）. After treatment， the counts of Lactobacillus and Bifidobacterium increased in both groups compared to before treatment（P＜0.05）， with the acupuncture-medication group showing higher counts than the acupuncture group（P＜0.05）； the counts of Enterococcus and Escherichia coli decreased in both groups compared to before treatment（P＜0.05）， with the acupuncture-medication group showing lower counts than the acupuncture group（P＜0.05）. The incidence of adverse reactions was 11.67%（7/60）in the acupuncture-medication group and 5.00%（3/60）in the acupuncture group，with no significant difference between the two groups （P＞0.05）. Conclusion： Brain-gut co-treatment acupuncture combined with Zuogui Decoction plus Xiaoyao Powder is effective in treating perimenopausal depression of kidney deficiency and liver stagnation type， significantly improving reproductive neuroendocrine hormone and neurotransmitter levels and regulating gut microbiota distribution.