Abstract: Peptide and protein biologics possess high specificity and high biological activity, but their poor stability and short plasma half-life have limited clinical application. One established strategy to increase half-life of therapeutic proteins is chemical conjugation of the biologic with PEG. Nevertheless, PEGylation technology has some drawbacks, so recombinant polypeptide mimetics of PEG have gradually developed in recent years. Pharmaceutically active protein can be fused with specific amino acid sequences using recombinant DNA technology, and then increase hydrodynamic volume or produce charge effect, which retards kidney filtration and eventually prolongs the half-life. This article mainly reviews kinds of polypeptides and the research progress in half-life extension of therapeutic proteins.