Functional oxide nanoparticles are extensively utilized in the last decades for biomedical purposes due to their unique functional properties. Nevertheless, their biodegradation mechanism by biological species, particularly by proteins at oxide/protein interfaces, still remains limited. Here, a systematic approaches is provided to investigate electrochemical behavior, electronic properties, and biodegradation mechanism of cobalt ferrite (CFO) and cobalt ferrite-bismuth ferrite (CFO-BFO) core-shell nanoparticles in apoferritin-containing media. Scanning Kelvin probe force microscopy results indicate that the presence of a thin shell (≈5 nm) of BFO on CFO causes a significant increase in surface potential. The potentiodynamic polarization measurements in different solutions showed higher anodic current densities for both samples when decreasing pH and increasing apoferritin concentration. Notably, CFO-BFO exhibits lower anodic current densities than CFO due to a slightly higher flat band potential and lower donor density distribution on CFO-BFO than on CFO, which results in lower electrochemical activity. Long-term monitoring reveals that biodegradation of both nanoparticles is accelerated by high apoferritin concentrations and acidic media, resulting in the decrease of electrochemical potentials and impedance values, and enhancement of metal ion release. Thus, this systematic biodegradation study can help to predict the lifespan and toxicity of these functional nanoparticles in biological environments.@en