In women, menopause refers to a series of physiological and mental symptoms of distress that result from a decrease in 17β-estradiol. In addition to the loss of fertility, the symptoms include facial flushing, depression, osteoporosis, sexual dysfunction, and genitourinary atrophy. Cirsium japonicum var. maackii is a perennial herbaceous species found in the mountains and fields of Korea, China, and Japan. The medicinal uses of C. japonicum include antioxidant, antidiabetic, antitumor, antifungal, and anti-inflammatory activities. We investigated the effect of C. japonicum extract in a rat model of menopause that exhibited rapid estrogen decline induced by ovariectomy (OVX rats). The rats were treated with C. japonicum extract for 10 weeks and the following parameters were measured: food intake, feed efficiency, body weight, total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, liver weight, 17β-estradiol, uterus weight, AST, ALT, bone mineral density (BMD), bone alkaline phosphatase, calcitonin, and osteocalcin. In OVX rats, the administration of 50 and 100 mg kg-1C. japonicum extract significantly decreased body weight, total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol and significantly increased 17β-estradiol and BMD. During the light/dark box test, the C. japonicum treatment group (100 mg kg-1) spent more time in the light chamber than in the dark area, which was reflective of their diurnal nature. Using a molecular docking simulation, we predicted the plausible binding mode of the active compounds of C. japonicum with the ligand binding domain of estrogen receptor (ER)-α and ER-β. These results showed that C. japonicum extract can treat the symptoms before and after the menopause.