Zinc-based nanoparticles (Zn-NPs), mainly zinc oxide (ZnO) NPs, have promising application in a wide area, but their potential harmful effects on environment and human health have been continuously raised together with their high dissolution rate. In this study, we coated the surface of ZnO NPs with phosphate (ZnP NPs) and sulfide (ZnS NPs) which have very low solubility in water, administered orally (0.5 and 1 mg/kg) to mice for 28 days, and then compared their biodistribution and toxicity. As expected, ZnO NPs were rapidly ionized in an artificial gastric fluid. On the other hand, ZnO NPs were more particlized in an artificial intestinal fluid than ZnP and ZnS NPs. After repeated dosing, all three types of Zn-NPs the most distributed in the spleen and thymus and altered the level of redox reaction-related metal ions in the tissues. We also found that three types of Zn-NPs clearly disturb tissue ion homeostasis and influence immune regulation function. However, there were no remarkable difference in distribution and toxicity following repeated exposure of three types of Zn-NPs, although Na+ and K+ level in the spleen and thymus were notably higher in mice exposed to ZnO NPs compared to ZnP and ZnS NPs. Taken together, we suggest that all three types of Zn-NPs may influence human health by disrupting homeostasis of trace elements and ions in the tissues. In addition, the surface transformation of ZnO NPs with phosphate and sulfide may not attenuate toxicity due to the higher particlization rate of ZnO NPs in the intestine, at least in part. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1363-1374, 2017.