With the rapid development of nanotechnology, personal care products with silver nanoparticles (Ag-NPs) or zinc oxide nanoparticles (ZnO-NPs) are being widely used because of their superior antibacterial efficacies. Biological fluids would thus inevitably interact with Ag-NPs or ZnO-NPs. Human tear fluid is an important model that was ignored in past studies, restricting the comprehensive understanding of the stability and health risks of Ag-NPs and ZnO-NPs. Herein, two simulated tear fluid models were examined, allowing us to understand potential transformations that can affect the properties and toxicity of Ag-NPs and ZnO-NPs. Both Ag-NPs and ZnO-NPs exhibited high chemical stability in the simulated tear fluid containing proteins even after an incubation time of 168 h due to the formation of biocoronae on the particles, resulting in inferior antibacterial activities of Ag-NPs and ZnO-NPs to E. coli . Nevertheless, Ag-NPs and ZnO-NPs could gradually transform into AgCl and Zn 5 (CO 3 ) 2 (OH) 6 respectively in the simulated tear fluid without protein, wherein AgCl or Zn 5 (CO 3 ) 2 (OH) 6 accounted for 59.7% of silver or 91.7% of zinc through a selective dissolution method established in this study. The size of AgCl particles was far smaller than that of pristine Ag-NPs, whereas Zn 5 (CO 3 ) 2 (OH) 6 exhibited a needle-crossed morphology with a large size compared to pristine ZnO-NPs. An enhanced antibacterial efficacy was observed for the transformed Ag-NPs relative to that for pristine Ag-NPs, since high concentrations of dissolved silver were detected in the culture medium with the transformed Ag-NPs. Compared to pristine ZnO-NPs, in contrast, the transformed ZnO-NPs showed moderate antibacterial activity to E. coli . In total, the chemical stability of Ag-NPs and ZnO-NPs in the simulated tear fluid was highly affected by the protein, which would further influence their antibacterial efficacies. The chemical stability of Ag-NPs and ZnO-NPs in simulated tear fluid was highly affected by proteins, which would further influence their antibacterial efficacies.