We conducted a double-blind, randomized, placebo-controlled trial to evaluate the effects of soy-derived isoflavone on blood glucose, lipid profiles, and sex hormones related to cardiovascular disease in Korean postmenopausal women. One hundred thirteen postmenopausal women were recruited from the Seoul metropolitan area. To confirm postmenopausal and gynecologic status, the subjects were clinically examined by a gynecologist using ultra sound and X-ray. Finally, 85 postmenopausal women whose follicle-stimulating hormone (FSH) levels were higher than 40 IU/ml were enrolled. Subjects received either 70 mg isoflavone or placebo capsules daily for 12 weeks. As a result, the values of fasting glucose, insulin and HOMA-IR, as well as those of TC, LDL-C, HDL-C and FFA, were not different between the groups after supplementation. However, triglyceride (TG) levels in the treatment group decreased significantly compared with those of the placebo group (p = 0.0215). The levels of luteinizing hormone (LH) significantly decreased in the treatment group (p = 0.027); however, the levels of FSH, estrone and estradiol were not changed after intervention. In conclusion, isoflavone supplement of 70 mg/day for 12 weeks decreased blood levels of TG and LH in Korean postmenopausal women.