There are a large number of incidental nanoparticles endowed with special activities and functions by their nano-scale structures in some traditional food systems, but the effects of the incidental nanoparticles on the human cells remain unclear. In the case study of freshwater clam soup and its incidental nanoparticles prepared by liquid chromatography, the cytotoxicity effects of freshwater clam soup and its nanoparticles on MDCK, Caco-2, L-02, and murine peritoneal macrophages were evaluated. Besides, the phagocytosis functions of murine peritoneal macrophages interacted with soup and its nanoparticles were also investigated. The results showed that freshwater clam soup and its incidental nanoparticles did not show apparent toxicity to the four cell within the concentration of 15.63-500.00μg/mL. Further study found that murine peritoneal macrophages could engulf freshwater clam soup incidental nanoparticles. They did not influence the membrane potential and phagocytosis function of the normal peritoneal macrophages but prevented the cells from the membrane hyperpolarization, mitochondrial oxidative stress, and phagocytosis suppression induced by AAPH-induced oxidative stress. The antioxidant analysis revealed that freshwater clam soup incidental nanoparticles exerted FRAP and ABTS antioxidant activity, but not ORAC antioxidant activity. The research results provided a scientific basis for further research on the physiological function and related mechanism of freshwater clam soup and its incidental nanoparticles.