<p>Micro-arc oxidation (MAO) is an effective approach to promote the surface properties of biomedical multi-principal element alloys (bio-MPEAs) as a new generation of bio-metals for hard tissue substitution. However, current understanding on the relationship between the microstructure and corrosion resistance of bio-MPEA-based MAO coatings is still limited. In this study, Ti, TiNbZr medium entropy alloy (MEA) and TiNbZrTaHf high entropy alloy (HEA) were selected as the substrate materials for MAO treatment. The results show that bio-MPEA-based MAO coatings are quite different from Ti-based MAO coatings in both thickness and microstructure. The overall thickness of MAO coatings is in an order of HEA ≈ MEA &gt; Ti, while the thickness of the inner layers follows the trend of MEA &gt; HEA &gt; Ti. The bio-MPEA-based MAO coatings are composed of an outer layer with nanocrystalline/amorphous composite structure and an amorphous inner layer, while Ti-based MAO coatings are consisted of an amorphous outer layer and an inner layer of rutile TiO₂. The corrosion resistance of MAO coatings is ranked as MEA &gt; HEA &gt; Ti, evidenced by the initial and long-term corrosion performance. Moreover, the in vitro experiments confirm the favorable cytocompatibility of all coatings. Together, the results indicate that the growth behavior and microstructure of MAO coatings on bio-MPEAs are distinct from those on Ti, which are responsible for their superior corrosion resistance.</p> Graphical abstract <p></p>