Micro/nanoscale carrier is a crucial component of the drug delivery system that enables to be well designed for improving the pharmacological and therapeutic properties of drug administration. Herein we systemically review a special vector of natural poly(amino acid) (PAA) that has been extensively applied in the controlled delivery of drug, protein and gene due to its excellent biocompatibility, controlled degradability, and flexible physicochemical modification. Natural PAA is a group of poly(ionic) molecules that present various biological roles and putative technical functions. The intention of this review is to thoroughly summarize three classic types of PAA involving anionic, cationic and neutral PAA as well as their applications on drug delivery systems.