Cerebral ischemic insult not only generates reactive oxygen species but increases oxidative stress and further cerebral injury. Curcumin is a natural polyphenol compound possesses antioxidant property. This study explored whether the neuroprotective mechanism of curcumin during cerebral ischemia is associated with the modulation of lipid peroxidation, the antioxidant superoxide dismutase (SOD), catalase (CAT), the essential element magnesium (Mg), zinc (Zn), selenium (Se), transition metal iron (Fe), copper (Cu), and toxic metal lead (Pb). Experimentally, a total of forty Sprague–Dawley male rats were used in the present study. Cerebral ischemia was induced by ligation of the right common carotid artery (RCCA) and the right middle cerebral artery (RMCA) for 1 hour. The prevention group was intraperitoneally injected with curcumin (100 mg/kg) once daily for consecutive 10 days before artery ligation. The right cerebral cortex was homogenized and the supernatants were harvested for biochemical analysis. Experimental results indicated that cerebral ischemic injury decreased SOD, CAT, Mg, Zn, Se, but increased MDA, Fe, Cu, and Pb. In turn, pretreating rats with curcumin before ischemic insult significantly reversed all biochemical results. Our findings suggest that curcumin attenuates cerebral ischemia-induced oxidative stress via modulating lipid peroxidation, antioxidant activity, essential elements, transition, and toxic metals. Crucially, the present results provide a new possibility for the therapeutic strategy of curcumin to chelate other neurotoxic metals.  (J Intern Med Taiwan 2022; 33: 448-458)