Platinum nanoparticles (NPs) are reported to mimic various antioxidant enzymes and thus may produce a positive biological effect by reducing reactive oxygen species (ROS) levels. In this manuscript, we report Pt NPs as an enzyme mimic of ferroxidase by depositing platinum nanodots on gold nanorods (Au@Pt NDRs). Au@Pt NDRs show pH-dependent ferroxidase-like activity and have higher activity at neutral pH values. Cytotoxicity results with human cell lines (lung adenocarcinoma A549 and normal bronchial epithelial cell line HBE) show that Au@Pt NDRs are taken up into cells via endocytosis and translocate into the endosome/lysosome. Au@Pt NDRs have good biocompatibility at NDR particle concentrations lower than 0.15 nΜ. However, in the presence of H2O2, lysosomelocated NDRs exhibit peroxidase-like activity and therefore increase cytotoxicity. In the presence of Fe2+, the ferroxidase-like activity of the NDRs protects cells from oxidative stress by consuming H2O2. Thorough consideration should be given to this behavior when employing Au@Pt NDRs in biological systems.[Figure not available: see fulltext.] © 2015 Tsinghua University Press and Springer-Verlag Berlin Heidelberg