Hyperglycemia-induced complications, the major causes of death in diabetes, are closely related to the elevated oxidative stress. Our previous study indicated that fruiting bodies of Ophiocordyceps sinensis attenuated polydipsia and hyperglycemia in diabetic rats. In this study, we further investigated whether the protective effects of O. sinensis on diabetes are associated with improved oxidative status in the circulation and target organs, the liver and kidneys. Male Wistar rats were fed with a semipurified diet supplemented with fruiting bodies (FB group, 1 g/day), carcass (CC group, 1 g/day), fruiting bodies and carcass (CF group, each 0.5 g/day), or placebo (DM and R groups) for 4 weeks (day 1 to 29). On day 15, animals were injected with nicotinamide (200 mg/kg) and streptozotocin (65 mg/kg) to induce diabetes. After the induction of diabetes, fasting blood glucose (FBG) was increased and the diabetes-increased FBG (day 15 to 26) was alleviated by the supplementation of fruiting bodies (p < 0.05, one-way ANOVA). In addition, the contents of vitamins A and C in the liver were significantly higher in the FB group, and the contents of glutathione in the liver and vitamin A and C in the kidneys were significantly higher in the FB, CC, and CF groups than in the DM group. The diabetes-increased glutathione peroxidase activity in the liver was decreased in the CF group. These results suggest that O. sinensis, especially fruiting bodies, may have antihyperglycemic activity associated with the alleviated oxidative stress in the liver and kidneys.