Aim To evaluate the impact of postmenopausal osteoporosis on thiol/disulfide homeostasis. Materials and methods A total of 75 participants were divided into two groups: Group 1 (n = 40) was composed of healthy postmenopausal women, and group 2 (n = 35) was composed of women with postmenopausal osteoporosis. Clinical findings and thiol/disulfide homeostasis were compared between the two groups. Results The disulfide/native thiol ratio was 8.6% +/- 3.6 in group 1 and 12.7% +/- 8.4 in group 2 (p = 0.04). The disulfide/native thiol percent ratio was significantly higher in group 2 after adjustment for the years since menopause and age (p24.9 in group 2 (p = 0.01). The native thiol/total thiol percent ratio was significantly lower in group 2 after adjustment for the years since menopause and age (p < 0.05). Conclusion Thiol/disulfide homeostasis shifted to the disulfide side independent of age and years since menopause in postmenopausal osteoporosis.