Menopause is considered to mean falling levels of ovarian estradiol and progesterone. Menopause syndrome can lead to hot flashes, headaches, and depression etc. Corni Fructus (CF) was used as a therapeutic herbal medicine for treating various diseases such as pain, diabetic nephropathy and tuberculosis. This study was conducted to evaluate the protective effects of CF in follicle depletion of a mice model using the industrial chemical 4-vinylcyclohexene diepoxide (VCD). VCD directly targets prenatal follicles. Mice were injected with VCD (160 mg/kg) daily for 15 days and administered CF 18 times after VCD injection. CF treatment reduced body weight, tail skin temperature, and uterus weight. In addition, CF treatment significantly decreased total cholesterol, low-density lipoprotein, low-density lipoprotein/high-density lipoprotein ratio, and osteocalcin levels as well as correcting skin temperature. These results support the therapeutic potential of CF for those who suffer from menopause symptoms.