Background The aims of this research were to document the nature of oxidative stress (OS) while taking an estrogen/progestagen-combined oral contraceptive (OC) and to evaluate the action of two different products composed of a combination of antioxidant, vitamins and natural products in physiological quantity and classified as antioxidant/food supplement. For this reason, the two products are classified as physiological modulators (PM), able to restore the balance between antioxidants and reactive oxygen species in the organism. Study Design The Reactive Oxygen Metabolites-derived compound test, a photometric assay that measures the hydroperoxides levels in biological fluids, was used to determine the OS. OS was analyzed every 3 days (from t 1 to t 27) for 28 days on 10 healthy volunteers during three successive OC treatment cycles with a contraceptive (Microgynon®: ethinylestradiol 50 mcg plus levonorgestrel 125 mcg). In the first cycle, the OC was administered by itself; in the successive two cycles, the OC was administered in association in an open crossover study with two different types of PMs with antioxidant action. The main difference in the composition of the two products is the presence/absence of catechins from green tea. Results With just OC treatment, all the volunteers showed an increase in the OS values from 240±22.3 (mean±SD) Carratelli Units. (normal value) up to values >400 Carratelli Units (severe OS), then returned to normal when the OC therapy was suspended. The concomitant use of the two PMs showed that only the product containing green tea catechins was able to reduce the OS values, on average, by approximately 50% ( t test p<.05). Conclusion We conclude that to control the OS generated by OC, specific types of physiological modulators are needed.