The article provides a comprehensive overview of the research progress on the PEGylation of therapeutic proteins and peptides (TPPs). PEGylation is a crucial strategy to enhance the stability, solubility, and pharmacokinetic properties of TPPs, addressing their limitations such as low solubility, poor stability, short half-life, and high immunogenicity. The review covers the physicochemical properties and classification of PEG and its derivatives, the sites modified by PEGylation in TPPs, and factors influencing the PEGylation process. It highlights typical cases of PEGylated TPPs, including antimicrobial peptides, interferons, asparaginase, and antibodies, demonstrating their enhanced efficacy and reduced immunogenicity. The article also discusses the future prospects of PEG-modified TPPs, emphasizing the need for further research to optimize PEGylation techniques, understand the impact on immune response, and explore innovative PEGylation strategies. The authors conclude by outlining key areas for future investigation to advance the field of TPPs and improve the development of more efficient and safer PEG-modified options.The article provides a comprehensive overview of the research progress on the PEGylation of therapeutic proteins and peptides (TPPs). PEGylation is a crucial strategy to enhance the stability, solubility, and pharmacokinetic properties of TPPs, addressing their limitations such as low solubility, poor stability, short half-life, and high immunogenicity. The review covers the physicochemical properties and classification of PEG and its derivatives, the sites modified by PEGylation in TPPs, and factors influencing the PEGylation process. It highlights typical cases of PEGylated TPPs, including antimicrobial peptides, interferons, asparaginase, and antibodies, demonstrating their enhanced efficacy and reduced immunogenicity. The article also discusses the future prospects of PEG-modified TPPs, emphasizing the need for further research to optimize PEGylation techniques, understand the impact on immune response, and explore innovative PEGylation strategies. The authors conclude by outlining key areas for future investigation to advance the field of TPPs and improve the development of more efficient and safer PEG-modified options.