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Currently, peptide drugs are widely used in clinical practice due to their characteristics of low therapeutic doses, minimal side effects, and ease of application. By modifying peptide molecules, altering their structure or introducing non-peptide structures, it is possible not only to reduce the effects of toxins but also to overcome the challenges associated with the synthesis of peptide drugs; this can be considered an optimization of peptide drug synthesis techniques. 1. Natural active peptide library for peptide drugs: Peptide drugs generally refer to short peptides consisting of 2–50 amino acids; longer sequences are classified as protein drugs. In terms of size, synthesis difficulty, selectivity, and activity, peptides occupy a middle ground between small-molecule drugs and biological macromolecule drugs. The Medici peptide synthesis research team focuses closely on the field of peptide drug research, striving to address the key issues that hinder the development and application of peptide drugs. To date, they have established a comprehensive system that covers everything from the synthesis of upstream non-natural amino acid building blocks, the modification of peptide drugs and their large-scale production, to downstream research on the signal transduction pathways and mechanisms of action of peptide drugs. The peptide drug development library includes endogenous and exogenous bioactive peptides. Although both can be developed directly into drugs, due to their inherent properties, chemical modifications are often required to endow them with characteristics suitable for drug development, in order to turn them into valuable medications. The research and development of peptide drugs has become one of the key areas in pharmaceutical chemistry. (1) Endogenous active peptides of peptide drugs: A considerable number of signaling molecules present in the body are peptides and proteins, and the onset and progression of many diseases are related to imbalances in these substances. Therefore, proteins and peptide-based drugs derived from the organisms themselves are receiving increasing attention; they are known as endogenous active peptides or proteins. Due to their extremely low levels in the body yet strong biological effects, as well as their wide distribution, bioactive peptides serve as natural lead compounds for the development of various drugs. (2) Exogenous bioactive peptides: Exogenous peptides represent another important source of bioactive peptides, particularly peptide toxins and antibiotics derived from animals, such as bee venom, snake venom, frog venom, conus toxins, etc. It has strong physiological effects and a wide range of actions, which has drawn considerable attention in drug development, especially in the fields of pain relief, anti-inflammation, anti-tumor therapy, and treatment of neurological diseases; there are numerous examples of compounds that have been developed into drugs as a result. 2. Advantages and disadvantages of peptide drugs Peptide drugs have their own advantages and disadvantages. Its advantages are: (1) Most peptide drugs derive from endogenous peptides or other natural peptides; therefore, their structures are well-defined and their mechanisms of action are clear ； (2) Compared with most ordinary small organic molecule drugs, peptide drugs have prominent advantages such as high activity, low dosages required, low toxic and side effects, and amino acids as their metabolic end products ； (3) Compared to proteins, smaller peptides have almost no immunogenicity ； (4) Peptide drugs can be chemically synthesized, offering high product purity and controllable quality. Its disadvantages are: (1) it is easily degraded and has a short half-life ； Poor bioavailability ； (2) Most of them cannot be taken orally; they are generally in injectable form, and appropriate administration methods need to be developed ； (3) Large-scale synthesis and separation/purification are difficult ； (4) Macropetides are immunogenic. 3. Optimization of peptide drug synthesis techniques: Researchers in China have focused on studying important endogenous peptides in the human body as well as custom-designed peptide molecules, and have carried out chiral synthesis of non-natural amino acids in order to overcome issues such as the relative simplicity of existing methods for chemically modifying peptide drugs and the limited range of structural units that can be modified. Furthermore, non-natural amino acids can also be introduced to improve the stability of peptide drugs ； Adopt a yin-yang balance strategy to enhance the ability of peptide drugs to cross the blood-brain barrier ； Based on the mechanism of action, novel peptide drugs are designed to reduce toxic side effects. Currently, computer-aided technologies can also be used to rationally design peptide candidate drugs. In the structural design of peptide analogs, modifying the amino acids at sites prone to enzymatic degradation can often also increase their stability. In our country, researchers have utilized artificially designed non-natural HIV fusion inhibitors; starting from their 3D structures and independent of natural ligand sequences, they have developed anti-HIV fusion peptides that prevent the formation of the HIV fusion envelope, thereby enabling early intervention in the control of the HIV virus ； Betaine was used to modify the N-termini of the model peptides GRRT and T20 in order to increase the water solubility of poorly soluble peptides and suppress peptide aggregation. Modifying the molecular structure of peptide drugs themselves is the fundamental way to alter their pharmacological activity and drug-likeness. An increasing number of peptide drugs possess structural features with multiple modifications; therefore, chemical modification has become an important aspect in the development of peptide drugs, and new approaches to modification warrant attention. Therefore, researchers can take advantage of these characteristics of peptide drugs to carry out structural design and chemical modification, thereby maximizing their advantages and overcoming or avoiding their disadvantages, so as to achieve the desired goals in research and development for specific indications.