In this study, we investigated the therapeutic effects of a novel formulation of low-dose calcium and vitamin D3, blended with Rehmannia glutinosa Libosch and Eleutherococcus senticosus Max (RE⁢), in postmenopausal women. The controls were given either a placebo or high dose calcium and vitamin D3 (Ca⁢D). Bone mineral density (BMD) in the L2-3 lumber spines and femur regions was assessed, and serum osteocalcin, bone-specific alkaline phosphatase (BALP), and cross-linked N-telopeptide of type I collagen (NTx) were used as markers of osteoblast and osteoclast activity. Furthermore, all variables were measured before and after 6 and 12 months of treatment. The osteocalcin level was higher in the RE⁢ group, and BALP was almost the same in all groups. Serum NTx was significantly decreased in the RE⁢ group after 12 months (p＜0.05). The NTx in the Ca⁢D and placebo groups showed no significant change. The decrease of femur BMD was further demonstrated in the placebo group, but significantly increased in the RE⁢ group after 6 and 12 months of treatment (p＜0.05). There were significant differences in the percent changes of femur BMD between the placebo and RE⁢ groups (p＜0.01) and Ca⁢D and RE⁢ groups (p＜0.05). The decrease of spine BMD in the placebo group was inhibited both in the Ca⁢D and RE⁢ groups, however, there was significant difference only between the placebo and RE⁢ groups (p＜0.05). These findings suggest that continuous oral therapy of the RE⁢ formulation reduces rapidly decreasing bone mineral density in postmenopausal women more effectively than high doses of calcium and vitamin D3 alone by inhibiting osteoclastic activity. Therefore, it seems that the RE⁢ has its own antiosteoporotic effects. We suggest larger clinical studies to determine the most efficacious dosage and benefits of this novel treatment.