Molecular hydrogen is an experimental therapeutic agent in biomedicine, however its effects on serum antioxidant markers are poorly described so far. Sixteen healthy men (age 24.6 ± 3.6 years, height 183.3 ± 4.4 cm; weight 83.5 ± 12. 5 kg) participated in this randomized, double blind, placebo-control pilot study. The participants were assigned to receive either 300 mL per day of oral hydrogen-rich water or placebo (tap water) for 4 weeks, and were evaluated at baseline, and following 4-weeks of intervention. Hydrogen-rich water intervention significantly improved serum activities of superoxide dismutase and glutathione as compared to the placebo (P < 0.05), while no differences were observed between groups for changes in catalase and glutathione peroxidase at 4-week follow-up. In addition, hydrogen-rich water notably reduced serum malondialdehyde levels at post-administration, with change being significantly different comparing to placebo (- 25.8% vs. 11.7%; P < 0.001). In conclusion, hydrogen-rich water might be recognized as a novel agent to prevent oxidative stress or minimize its damaging effects by enhancing antioxidant enzymes capacity in healthy men. However, a mechanism of its antioxidant action remains unknown.