Molybdenum trioxide (MoO 3 ) has over the years captivated significant scientific attention, mainly in infection prevention and cancer treatment. However, as cytotoxicity of the compound poses a great concern, herein we test the hypothesis that MoO 3 in the form of commercially available particles triggers cytotoxic responses yet may also act as an antioxidant. In doing so, human-derived macrophages were exposed to variously concentrated (50−500 μM) MoO 3 particle suspensions and examined from the cytocompatibility point of view. Cytotoxicity assays were coupled with cell morphology characterization via confocal laser scanning microscopy imaging, reactive oxygen species (ROS) detection, and flow cytometry for macrophage polarization analysis. Moreover, the DPPH assay for radical scavenging ability was performed. Generally, dose-dependent cytotoxicity of MoO 3 was noted, with concentrations up to 100 μM being well-tolerated by macrophages. The particles demonstrated antioxidant activity, as confirmed by their ability to scavenge DPPH radicals. However, at the highest concentration studied, i.e., 500 μM, MoO 3 became highly cytotoxic and triggered cell death, as evidenced by alterations in cell shape and abnormal ROS production. Overall, the antioxidative and cytotoxic character of MoO 3 particles at low and high concentrations, respectively, was highlighted. The findings pave the way for future studies in the area of MoO 3 -based materials and validate their usefulness for biomedical purposes, as in antioxidant-based treatments.