Purpose of investigation: Oxidative stress impacts many age-related degenerative processes, such as in postmenopausal bone loss and in antioxidant defenses that are significantly decreased in elderly osteoporotic women. The authors evaluated the effect of oral supplementation with antioxidant agents containing alpha lipoic acid (ALA) on bone mineral density (BMD) of osteopenic postmenopausal women. Materials and Methods: Fifty postmenopausal women with osteopenia (– 2.5 < T-score < – 1) were prospectively enrolled and randomly assigned to orally receive ALA and other antioxidant agents (vitamin C, vitamin E, and selenium) plus calcium and vitamin D3 (n = 25), or only calcium and vitamin D3 (n = 25). The BMD was estimated at baseline and after 12 months of treatment by heel quantitative ultrasonometry (QUS). Results: Forty-four patients completed the one-year study: 23 in the ALA group, 21 in the control group. The treatment of ALA group led to a better estimated BMD compared to the control group (0.401 ± 0.026 vs 0.388 ± 0.025 g/cm2), although this difference barely achieved a statistical significance (p = 0.048). Conclusion: These findings, although in a small population, could suggest that oral supplementation with antioxidant agents containing ALA may mitigate bone loss in osteopenic postmenopausal women.