Objective To evaluate the clinical therapeutic efficacy and safety of modified Erzhi granules (MEG) in patients with menopause-related vulvovaginal atrophy (VVA). Methods This randomized, double-blind, placebo-controlled study comprised two groups, including the treatment and control groups. Patients receive MEG and placebo for 12 weeks, respectively. Vaginal health score (VHS), vaginitis score, vaginal maturation index (VMI), female sexual function index (FSFI), and modified Kupperman Index (modified KI) were used as efficacy endpoints and assessed at baseline, 4, 8, and 12 weeks during administration, and 4 weeks after drug withdrawal. At baseline and 12 weeks, serum estradiol (E2), follicle stimulating hormone (FSH), pelvic ultrasound, breast ultrasound, and other safety parameters were measured, recording adverse events. Results At 12 weeks, VHS, percentage of superficial cells in the vaginal epithelium and FSFI were significantly increased, while vaginitis score, percentage of basal cells in the vaginal epithelium, and modified KI were significantly decreased in comparison with baseline and control group (all P<0.05); these differences persisted for up to 4 weeks after drug withdrawal. The placebo group showed no significant change during treatment compared with baseline values (p>0.05). Serum E2 and FSH levels, endometrial thickness, and breast thickness in all patients were within the normal ranges before and after treatment, with no serious adverse reactions observed. Conclusion MEG significantly alleviates menopause-related vulvovaginal atrophy, with no overt adverse effects on the endometrium, breast, hepatic, and renal functions.