The principal objective of this study was to assess the effects of soy isoflavone supplementation on bone mineral density in 36 female college students with osteopenia for 12 weeks. The subjects were divided into three groups on the basis of bone mineral density. The experimental groups were provided supplements of either 80 mg of isoflavone (Iso-80) or 40 mg of isoflavone (Iso-40). To the placebo group, 40 mg of powdered glutinous rice was administered. It was determined that many subjects with osteopenia evidenced lower levels of activity as compared to the control group. Isoflavone supplementation was more effective in controlling total cholesterol and LDL-cholesterol than was observed in the placebo group. We noted no significant differences in serum osteocalcin concentration between Iso-40 and the placebo group, but significant differences in osteocalcin concentration were detected between Iso-80 and the placebo group. Bone quality indices (BQI) were correlated positively with mineral content, lean body mass, muscular mass, and blood components including albumin, Ca, Mg, ALPase, and osteocalcin. Both Iso-40 and Iso-80 supplementation for 12 weeks significantly increased protein and mineral content in the body. As lower intakes of Ca and folate were noted in the subjects, emphasis should be given to adequate intakes of these nutrients in the subjects. In conclusion, 12 week isoflavone supplementation in young females with osteopenia exerted positive effects on bone mineral density and bone turnover markers.