Introduction and objective Protective antioxidative effects of melatonin have been repeatedly documented in experimental and clinical studies. One of the most spectacular exogenous prooxidative agents is cigarette smoking. The aim of the study was to evaluate the level of oxidative damage to membrane lipids (lipid peroxidation; LPO) in blood serum, and in epidermis exfoliated during microdermabrasion collected from former-smokers who were treated with melatonin. Material and Methods The study was performed in postmenopausal women. Ninety (90) female volunteers, aged 46–67 years, were enrolled. Two major groups, i.e. never-smokers (n=44) and former-smokers (n=46), were divided into: Control, melatonin topical skin application, Restructurer (containing antioxidants) topical skin application, and melatonin oral treatment. Microdermabrasion was performed at point ‘0’, after 2 weeks, and after 4 weeks of treatment. The following parameters were measured: LPO in blood serum, LPO in epidermis exfoliated during microdermabrasion, and skin biophysical characteristics, such as sebum, moisture, elasticity, and pigmentation. Malondialdehyde+4-hydroxyalkenals level (LPO index) was measured spectrophotometrically. Results Melatonin oral treatment significantly reversed the increased serum LPO level in former-smokers already after 2 weeks of treatment. In a univariate regression model, LPO blood level constituted the only independent factor negatively associated with melatonin oral treatment. After 4 weeks of treatment, melatonin given orally increased skin sebum, moisture and elasticity levels, and melatonin applied topically increased sebum level. Conclusions Exogenous melatonin reverses the enhanced oxidative damage to membrane lipids and improves skin biophysical characteristics in former-smokers.