The self-assembly behavior of polypeptides is common in nature. Compared with monopeptides, polypeptide-based self-assembled nanomaterials with ordered structures have good thermal stability, mechanical stability, semi-conductivity, piezoelectric and optical properties. In recent years, the self-assembly of polypeptides has become a hot topic in the material science and biomedical field. By reasonably adjusting the molecular structure of the polypeptide and changing the external environment of the polypeptide, the polypeptide can be self-assembled or triggered by non-covalent bonding forces such as hydrogen bond, hydrophobicity, and π - π accumulation to form specific polypeptide assemblies such as nanoparticles, hydrogels, nanofibers, and micelles. Due to good biocompatibility and controllable degradability, polypeptide-based self-assembled nanomaterials have been widely used in the fields of nanotechnology, imaging technology, biosensor, and biomedical science. As a new drug delivery system, the polypeptide-drug conjugate has the advantages of low toxicity, high efficiency, enhanced drug stability, and avoiding side effects. This paper reviews the research progress of polypeptide-drug self-assembly nanostructure in recent years. Several structural models of polypeptide self-assembly technology and the mechanism of polypeptide self-assembly are introduced. Then the assembly form of polypeptide-drug self-assembly and the application of self-assembly compound therapy is described.