The present study was performed to investigate the effects of equol on oxidative stress and the antioxidant defense system in the livers of mice. Mice were orally administered equol at either 5 or 25 mg/kg body weight/day for 1, 3, or 7 wk. Equol administration significantly inhibited biomarkers of oxidative stress (thiobarbituric acid-reactive substances value, carbonyl content, and serum 8-OH-dG) at all doses and for all durations of administration, and this phenomenon was most pronounced at 3 wk. Moreover, catalase and total superoxide dismutase (SOD) activities and their mRNA expression were significantly increased by equol. Although equol increased the glutathione peroxidase (GSH-px) activity in mice treated with equol for 1 wk, long-term administration of equol (7 wk) caused a decrease in the ratio of reduced/oxidized glutathione (GSH/GSSG) and the activities of GSH-px and glutathione reductase (GR). Taken together, these results suggest that equol may act as an antioxidant through an inhibition of oxidative stress and stimulation of catalase and SOD, but can also cause prooxidant effects such as reduction of the GSH/GSSG ratio, depending on the treatment period.