Abstract: In recent years, researchers on nanomaterials in the fields of cell regulation and tissue regeneration have gradually deepened due to their small size and susceptibility to phagocytosis. Among them, melanin nanoparticles have received significant attention due to their wide range of sources and good performance. This article reviews the progression of melanin nanoparticles in regulating macrophage phenotype. In this article, the effects of melanin nanoparticles on M1 and M2 macrophages are discussed, the possible regulatory mechanisms are analyzed, and then the prospects for clinical application are prospected. With the deepening of research, the application of melanin nanoparticles in the field of biomedicine will be more extensive.