Objective To observe the clinical effect of electroacupuncture (EA) treatment for mild to moderate depression in peri-menopausal period. Methods Sixty patients diagnosed with mild to moderate depression in perimenopausal period were randomized into EA group (n = 30) and control group (n = 30, with oral administration of Escitalopram Oxalate Tablets). The curative effect was evaluated by Hamilton Depression Scale (HAMD-17). Results After 12-week treatment, the two treatment methods had significant effect on the patients. In the drug control group, 6 cases were markedly effective, 12 cases were effective, 12 cases were ineffective, the total effective rate was 60%. In the EA group, 25 cases were markedly effective, 2 cases were effective, 3 cases were ineffective, the total effective rate was 90%, the EA group was significantly superior to the control group (P < 0.05). After treatment, the total scores of HAMD-17 in the two groups were significantly lower than those before treatment, and the total score of HAMD-17 in the EA group was lower than that in the control group (P < 0.05). The improvement degree of the scores of depression symptom and difficulty in falling asleep in the EA group was significantly different from that in the control group (P < 0.05). Conclusions EA treatment can effectively interfere with mild to moderate depression in peri-menopausal period, improve the clinical symptoms and the quality of life.