Therapeutic peptides are a class of pharmaceutical agents composed of amino acids, with molecular weights ranging from 500 to 5000 Da. Since the discovery of insulin in 1921, therapeutic peptides have been developed to treat various diseases, with over 80 peptide drugs approved globally. The development of peptide drugs has become a major focus in pharmaceutical research. The first half of the 20th century saw the discovery of several life-saving bioactive peptides, such as insulin and adrenocorticotrophic hormone, which were initially isolated from natural sources. The discovery and development of insulin, a 51-amino acid peptide, marked a significant achievement in drug discovery. It was first isolated by Frederick Banting in 1921 and further developed by Frederick and Charles Best, becoming the first commercial peptide drug. However, the production of human insulin during the 20th century could not keep up with the high market demand, and animal-derived insulins, such as bovine and porcine insulin, dominated the insulin market for almost 90 years until they were replaced by recombinant insulin. From the 1950s to the 1990s, more peptide hormones and their receptors with therapeutic potential were identified and characterized. The technologies used for protein purification and synthesis, structure elucidation, and sequencing made substantial progress, accelerating the development of peptide drugs, leading to nearly 40 peptide drugs being approved worldwide. Synthetic peptides such as synthetic oxytocin, synthetic vasopressin, and recombinant human insulin began to be developed in addition to natural peptides. Peptide drug development entered a new era with the advent of the 21st century, as advances in structural biology, recombinant biologics, and new synthetic and analytic technologies significantly accelerated the process. A sophisticated system of peptide drug development has been established, including peptide drug discovery, drug design, peptide synthesis, structural modification, and activity evaluation. A total of 33 non-insulin peptide drugs have been approved worldwide since 2000. These peptide drugs are no longer simply hormone mimics or composed simply of natural amino acids. For example, enfuvirtide is a 36-amino acid biomimetic peptide mimicking human immunodeficiency virus (HIV) proteins used in combination therapy for the treatment of HIV-1; ziconotide is a neurotoxic peptide derived from the cone snail Conus magus, which was approved in 2004 and is used to manage severe chronic pain; teduglutide is a glucagon-like peptide 2 (GLP-2) analogue used to treat short bowel syndrome; and liraglutide is a chemically synthesized analogue of human glucagon-like peptide 1 (GLP-1), made by attaching a C-16 fatty acid (palmitic acid)Therapeutic peptides are a class of pharmaceutical agents composed of amino acids, with molecular weights ranging from 500 to 5000 Da. Since the discovery of insulin in 1921, therapeutic peptides have been developed to treat various diseases, with over 80 peptide drugs approved globally. The development of peptide drugs has become a major focus in pharmaceutical research. The first half of the 20th century saw the discovery of several life-saving bioactive peptides, such as insulin and adrenocorticotrophic hormone, which were initially isolated from natural sources. The discovery and development of insulin, a 51-amino acid peptide, marked a significant achievement in drug discovery. It was first isolated by Frederick Banting in 1921 and further developed by Frederick and Charles Best, becoming the first commercial peptide drug. However, the production of human insulin during the 20th century could not keep up with the high market demand, and animal-derived insulins, such as bovine and porcine insulin, dominated the insulin market for almost 90 years until they were replaced by recombinant insulin. From the 1950s to the 1990s, more peptide hormones and their receptors with therapeutic potential were identified and characterized. The technologies used for protein purification and synthesis, structure elucidation, and sequencing made substantial progress, accelerating the development of peptide drugs, leading to nearly 40 peptide drugs being approved worldwide. Synthetic peptides such as synthetic oxytocin, synthetic vasopressin, and recombinant human insulin began to be developed in addition to natural peptides. Peptide drug development entered a new era with the advent of the 21st century, as advances in structural biology, recombinant biologics, and new synthetic and analytic technologies significantly accelerated the process. A sophisticated system of peptide drug development has been established, including peptide drug discovery, drug design, peptide synthesis, structural modification, and activity evaluation. A total of 33 non-insulin peptide drugs have been approved worldwide since 2000. These peptide drugs are no longer simply hormone mimics or composed simply of natural amino acids. For example, enfuvirtide is a 36-amino acid biomimetic peptide mimicking human immunodeficiency virus (HIV) proteins used in combination therapy for the treatment of HIV-1; ziconotide is a neurotoxic peptide derived from the cone snail Conus magus, which was approved in 2004 and is used to manage severe chronic pain; teduglutide is a glucagon-like peptide 2 (GLP-2) analogue used to treat short bowel syndrome; and liraglutide is a chemically synthesized analogue of human glucagon-like peptide 1 (GLP-1), made by attaching a C-16 fatty acid (palmitic acid)