In the present study, ZnS and ZnO quantum dots (QDs) were synthesized via an all-aqueous process with polyethylene glycol (PEG) chains on their surface, and their toxicity as well as biodistribution were evaluated. No haemolysis occurred at a high concentration of 1600 µg/mL in vitro haemolytic assay, which demonstrated that the QDs-PEG displayed good blood compatibility. Following intravenous administration at 2, 6, and 20 mg/kg of the QDs-PEG in mice, the biodistribution, excretion and biocompatibility were characterized at 1 h, 24 h and 7 days, respectively. Quantitative analysis results indicated that the biodistribution trend of ZnS QDs-PEG was similar to that of ZnO QDs-PEG. The QDs-PEG were mainly trapped in the lung and liver, and almost removed from blood within 1 h. QDs-PEG were primarily excreted in faeces at the 2 and 6 mg/kg doses. Coefficients, haematology, blood biochemistry and histopathology results indicated that the QDs-PEG were safe and biocompatible.