BACKGROUND It is well known that cerium oxide nanoparticles (CeNPs) have intense antioxidant activity. The antioxidant property of CeNPs are widely used in different areas of research, but little is known about the oxidative damage of Cu2+ associated with Type II diabetes mellitus (T2DM). MATERIAL AND METHODS In our research, the function of CeNPs was tested for its protection of β-cells from the damage of Cu2+ or H2O2. We detected hydroxyl radicals using terephthalic acid assay, hydrogen peroxide using Amplex Ultra Red assay, and cell viability using MTT reduction. RESULTS We found that CeNPs can persistently inhibit Cu2+/H2O2 evoked hydroxyl radicals and hydrogen peroxide in oxidative stress of β-cells. CONCLUSIONS CeNPs will be useful in developing strategies for the prevention of T2DM.