The article provides a comprehensive review of the development and applications of therapeutic peptides. It highlights the progress in peptide drug discovery, production, and modification, emphasizing the advantages and drawbacks of peptides as pharmaceutical agents. The review covers the historical development of peptide drugs, from the discovery of insulin to the current advancements in peptide synthesis and modification techniques. Key topics include the rational design of peptides based on Protein-Protein Interactions (PPIs), phage display technology for identifying peptide ligands, and the use of genetic code expansion to incorporate non-canonical amino acids into peptides. The article also discusses the challenges and opportunities in peptide drug development, such as membrane permeability and in vivo stability, and explores the potential of covalent peptide/protein drugs. Overall, the review underscores the significant role of peptides in modern pharmaceuticals and the ongoing efforts to overcome their inherent limitations.The article provides a comprehensive review of the development and applications of therapeutic peptides. It highlights the progress in peptide drug discovery, production, and modification, emphasizing the advantages and drawbacks of peptides as pharmaceutical agents. The review covers the historical development of peptide drugs, from the discovery of insulin to the current advancements in peptide synthesis and modification techniques. Key topics include the rational design of peptides based on Protein-Protein Interactions (PPIs), phage display technology for identifying peptide ligands, and the use of genetic code expansion to incorporate non-canonical amino acids into peptides. The article also discusses the challenges and opportunities in peptide drug development, such as membrane permeability and in vivo stability, and explores the potential of covalent peptide/protein drugs. Overall, the review underscores the significant role of peptides in modern pharmaceuticals and the ongoing efforts to overcome their inherent limitations.