Vitiligo is a multifactorial disorder commonly associated with hypo-/depigmentation in the skin and may influence both children and adults psychologically because of the notable leopard-skin-like appearance. This study was designed to investigate the thiol/disulfide homeostasis in patients with generalized vitiligo and to determine its relationship with some of the demographical characteristics. Seventy-six generalized vitiligo patients and 67 healthy individuals were included in the study. Blood serum native thiol, disulfide and total thiol concentrations, together with some hematological parameters, were determined. Results demonstrated that native and total thiol contents, and their ratios, were significantly lower in vitiligo patients. Disulfide/native thiol and disulfide/total thiol ratios were significantly higher in the patient group. Progressivity of the disease strongly regulated the thiol/disulfide homeostasis in such a way that active vitiligo patients had reduced native and total thiol levels but increased disulfide/native thiol and disulfide/total thiol ratios. Moreover, there was a statistically significant negative correlation between both duration of the vitiligo and native and total thiol contents. As these results clearly demonstrated that thiol/disulfide homeostasis was shifted toward disulfide formation in patients with generalized vitiligo, determining the dynamic nature of thiol/disulfide homeostasis can be used to monitor disease progression.