In the present investigation we report the protective potential of some herbal hypoglycemic agents on antioxidant status and levels of metal ions in streptozotocin-induced diabetic rats. Furthermore, in vitro antioxidant activity of the herbs was also evaluated. Induction of diabetes mellitus in rats caused an increase in blood lipid peroxide levels that was associated with the reduced activity of red blood cell (RBC) antioxidant enzymes--namely, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase--along with depletion of plasma reduced glutathione (GSH) and copper, zinc, iron, magnesium, and selenium levels. Oral treatment of diabetic rats with Allium sativum, Azadirachta indica, Momordica charantia, and Ocimum sanctum extracts (500 mg/kg of body weight) not only lowered the blood glucose level but also inhibited the formation of lipid peroxides, reactivated the antioxidant enzymes, and restored levels of GSH and metals in the above-mentioned model. The herbal extracts (50-500 microg) inhibited the generation of superoxide anions (O(2)(-.)) in both enzymatic and nonenzymatic in vitro systems. These preparations also inhibited the ferrous-sodium ascorbate-induced formation of lipid peroxides in RBCs. The in vivo and in vitro protective effects of the above-mentioned herbal drugs were also compared with that of glibenclamide. On the basis of our results, we conclude that the above-mentioned herbal plants not only possess hypoglycemic properties, but they also decrease oxidative load in diabetes mellitus. Therefore, we propose that long-term use of such agents might help in the prevention of diabetes-associated complications. However, the extrapolation of these results to humans needs further in-depth study.