Manganese-based nanozymes have been widely used in the field of cell protection due to their various enzyme-mimicking activities, but their effect on the mechanical properties of cells is not yet known. Here, bovine serum albumin-modified Mn3O4 nanoparticles (BSA-Mn3O4 NPs) with good biocompatibility were synthesized by a one-step biomineralization method using BSA as a template. BSA-Mn3O4 NPs possess scavenging activity against superoxide free radicals (O2˙-), hydroxyl radicals (˙OH) and hydrogen peroxide (H2O2). The excellent reactive oxygen species (ROS) scavenging activity of BSA-Mn3O4 NPs enables them to effectively reduce the intracellular ROS level, thus mitigating the damage of oxidative stress on human umbilical vein endothelial cells (HUVECs). Subsequently, the intracellular antioxidant mechanism of the BSA-Mn3O4 NPs was further investigated. The results show that the BSA-Mn3O4 NPs could inhibit the depolymerization of F-actin, help cells maintain their normal morphology, and reduce the decrease in Young's modulus of cells caused by oxidative stress.