Oxidative stress plays an important role in the development of vitiligo. The aim of our study was to assess the effect of oral vitamin supplementation with antioxidant activity on the effectiveness of the vitiligo treatment. The study group consisted of 46 patients suffering from nonsegmental vitiligo for over a year. Before and after the therapy, the clinical advancement of the disease (VASI) and impairment of quality of life (DLQI) were assessed in all patients, and the activities of selected antioxidant enzymes (SOD, CAT, and GPx), lipid peroxidation products (MDA), and vitamins A and E were determined. Each patient was randomly assigned to one of three therapeutic groups: FOTO (UVB therapy at 311 nm, 3x a week for 4 months), WIT (oral antioxidant supplementation‐vitamin A + E at a dose of 5000 IU of retinol and 400 mg of tocopherol), and FOTO + WIT (combination therapy). After the treatment, an increase in all antioxidant enzymes and a decrease in the concentration of malondialdehyde in patients were noted, regardless of the therapeutic method used. The greatest improvement in the repigmentation of skin lesions was achieved in patients treated with combined therapy (VASI −6.95 ± 4.69, p < 0.01, DLQI −1.90 ± 2.77, p = 0.011). The burden of patients with risk factors for oxidative stress turned out to be associated with a greater severity of the disease process, and a longer period of disease was positively correlated with a reduction in the quality of life in patients.