Abstract: Peptides have been extensively used in the fields of gene/drug delivery and disease targeting therapy. However, natural peptides are sensitive to protease digestion with short circulatory half-lives in vivo. Many studies on structural modifications of peptides have been reported to improve the delivery or therapeutic effect. In this review we focus on the recent literature on peptide stability in accordance with different structural modifications and summarize the methods and influential factors that are involved in the improvement of stability and half-life in vivo. This review will provide the scientific basis and theoretical references for further investigations and applications in vivo.