Abstract： Objective： To observe the clinical efficacy of Chinese medicinal foot bath combined with Liuzijue exercise under the guidance of midnight-noon ebb-flow theory in the treatment of patients with perimenopausal depression. Methods：A total of 60 patients with perimenopausal depression treated at Tonglu Second People′s Hospital from July 2024 to December 2025 were selected and randomly divided into the observation group and the control group using the random number table method，with 30 cases in each group. The observation group received Chinese medicinal foot bath （administered at the Hai period，9-11 PM） combined with Liuzijue Daoyin exercise （administered at the Xu period，7-9 PM） guided by the midnight-noon ebb-flow theory，while the control group was treated with Venlafaxine Hydrochloride Sustained-Release Capsules. Both groups were treated continuously for 12 weeks. The modified Kupperman score，Pittsburgh Sleep Quality Index （PSQI） score，Hamilton Depression Scale-17 （HAMD-17） score， and reproductive endocrine hormone levels [estradiol （E2）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）] were compared between the two groups before and after treatment， and the incidence of adverse reactions was recorded. Results： After treatment， the modified Kupperman scores and HAMD-17 scores in both groups decreased compared with those before treatment （P＜0.05），and both scores in the observation group were lower than those in the control group （P＜0.05）. After treatment，PSQI scores in both groups decreased compared with those before treatment （P＜0.05），and the PSQI score in the observation group was lower than that in the control group （P＜ 0.05）. After treatment，FSH and LH levels in both groups decreased compared with those before treatment （P＜0.05）， while E2 levels increased compared with those before treatment （P＜0.05）； the observation group showed lower FSH and LH levels （P＜0.05） and higher E2 level （P＜0.05） than the control group. During treatment，no serious adverse events occurred in either group. Conclusion：Under the guidance of the midnight-noon ebb-flow theory，application of Chinese medicinal foot bath combined with Liuzijue exercise for perimenopausal depression can effectively improve depressive symptoms， perimenopausal symptoms， and sleep quality， and regulate reproductive endocrine hormone levels，with good safety.