CuInS/ZnS-PEG quantum dots (QDs) are among the most widely used near infrared non-cadmium QDs and are favored because of their non-cadmium content and strong tissue penetration. However, with their increasing use, there is great concern about whether exposure to QDs is potentially risky to the environment and humans. Furthermore, toxicological data related to CuInS/ZnS-PEG QDs are scarce. In the study, we found that CuInS/ZnS-PEG QDs (0-100 μg/mL) could internalize into human LAD2 mast cells without affecting their survival rate, nor did it cause degranulation or release of IL-8 and TNF-α. However, CuInS/ZnS-PEG QDs significantly inhibited Substance P (SP) and LL-37-induced degranulation and chemotaxis of LAD2 cells by inhibiting calcium mobilization. Lower concentrations of CuInS/ZnS-PEG QDs promoted the release of TNF-α and IL-8 stimulated by SP, but higher concentrations of CuInS/ZnS-PEG QDs significantly inhibited the release of TNF-α and IL-8. On the other hand, CuInS/ZnS-PEG QDs promoted LL-37-mediated TNF-α release from LAD2 cells in a dose-dependent manner from 6.25 to 100 μg/mL, while release of IL-8 triggered by LL-37 was dose-dependently inhibited within a dose concentration of 12.5-100 μg/mL. Collectively, our data demonstrated that CuInS/ZnS-PEG QDs differentially mediated human mast cell activation induced by SP and LL-37.