Zinc oxide nanoparticles (ZnO NPs) are widely used as food additives, especially in nutritional foods. However, many reports have demonstrated their toxicity in humans and other biological systems. Our study has confirmed that ZnO NPs can induce apoptosis and oxidative damage on human gastric epithelium cells (GES-1). Caseinophosphopeptides (CPP) are also used as functional food additives that sequester prooxidant metals and scavenge free radicals. Herein, we investigate the combined cytotoxicity of ZnO NPs and CPP for the first time. The results show that CPP protects GES-1 cells from oxidative stress induced by ZnO NPs, decreases reactive oxygen species, diminishes the level of malondialdehyde, increases the content of glutathione and improves the activity of superoxide dismutase. Therefore, CPP can protect GES-1 cells against ZnO NP induced injury through the down-regulation of oxidative stress.