Like any typical food system, bone soup (or broth), a traditional nourishing food in many cultures, contains a colloid dispersion of self-assembled micro/nano-particles. Food ingestion results in the direct contact of food colloidal MNPs with immune cells. Will they ever interact with each other? To answer the question, MNPs and NPs were separated from porcine bone soup and labeled with Nile Red, and their uptake by murine oral macrophages and its consequent effects were investigated. Colloidal particle samples of UF-MNPs and SEC-NP were prepared from porcine bone soup by ultrafiltration (UF) and size-exclusion chromatography, respectively. Their mean hydrodynamic diameters were 248 ± 10 nm and 170 ± 1 nm with dominant composition of protein and lipid. Particles in both samples were found to be internalized by oral macrophages upon co-incubation at particle/cell ratios of 14,000/1. In normal oral macrophages, the particle uptake exerted influence neither on the cellular cytosolic membrane potential (Vmem) nor mitochondrial superoxide level, as were indicated with fluorescent dyes of DiBAC4(3) and MitoSOX Red, respectively. However, when oral macrophages were challenged by peroxyl radical inducer AAPH, the engulfment of UF-MNPs and SEC-NPs mitigated the peroxyl radical induced membrane hyperpolarization effect by up to 70%, and the suppression on the oxygen respiration in mitochondria by up to 100%. Those results provide evidence of the direct interaction between food colloidal particles with immune cells, implying a possible new mode of food-body interaction.