Polypeptides have attracted considerable attention in recent decades due to their inherent biodegradability and tunable cytocompatibility. Macromolecular design in conjunction with rational monomer composition can direct architecture, self-assembly and chemical behavior, ultimately guiding the choice of appropriate application within the biomedical field. This review focuses on the applications of polypeptides alongside the synthetic advances in the ring opening polymerization of α-amino acid N-carboxyanhydrides achieved in the past five years. Key architectures obtained through NCA ROP or in combination with other polymerization methods are reviewed, as these play an important role in the wide range of applications towards which polypeptides have been applied.