Increased levels of oxidative stress due to excessive production of reactive oxygen species are involved in the pathogenesis of periodontitis. Studies suggest a negative association between plasma vitamin C level and the severity of periodontitis. We hypothesized that increases in plasma vitamin C levels after vitamin C intake might clinically reduce gingival oxidative stress in a rat periodontitis model. A ligature was placed around rat mandibular molars for 4 weeks to induce periodontitis, and the rats were then given drinking water with or without 1 g/L vitamin C for 2 weeks after the ligature was removed. The periodontitis-induced rats showed a 149% increase in 8-hydroxydeoxyguanosine level and a 40% decrease in reduced:oxidized glutathione ratio in gingival tissue. Vitamin C intake induced a 175% increase in plasma vitamin C level, resulting in an improvement in the gingival 8-hydroxydeoxyguanosine level (decreased) and in the reduced:oxidized glutathione ratio (increased). Furthermore, in ligature-induced periodontitis lesions, gene expression encoding inflammation, including interleukin-1 alpha and interleukin-1 beta, was more than twofold down-regulated by vitamin C intake. The results suggest that systemic administration of vitamin C could be clinically beneficial in improving periodontitis-induced oxidative stress by down-regulating inflammatory gene expression.