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 drawn much attention due to their wide range of sources and good performance. The progression of melanin nanoparticles in regulating macrophage phenotype is reviewed, the effects of melanin nanoparticles on M1 and M2 macrophages and the possible regulatory mechanisms are discussed and analyzed, and then the prospects for clinical application are prospected in this article.