This review summarizes recent progress in the PEGylation of therapeutic proteins and peptides (TPPs). PEGylation, a chemical modification technique, enhances the stability, solubility, and pharmacokinetic properties of TPPs, addressing challenges such as rapid clearance, immunogenicity, and enzymatic degradation. The review discusses the physicochemical properties and classification of PEG and its derivatives, the main sites of PEGylation in TPPs, and factors influencing the PEGylation process. It highlights notable cases of PEG-modified TPPs, including antimicrobial peptides (AMPs), interferon, asparaginase, and antibodies, and analyzes the current development status and future prospects of PEGylated TPPs. The review emphasizes the advantages of PEGylation, such as improved solubility, stability, permeability, and pharmacokinetic properties, while also addressing potential drawbacks like reduced bioactivity and limited biodegradability. The study concludes that PEGylation holds significant potential for enhancing the therapeutic applications of TPPs, with ongoing research aiming to optimize PEGylation strategies and explore new approaches to improve drug efficacy and safety.This review summarizes recent progress in the PEGylation of therapeutic proteins and peptides (TPPs). PEGylation, a chemical modification technique, enhances the stability, solubility, and pharmacokinetic properties of TPPs, addressing challenges such as rapid clearance, immunogenicity, and enzymatic degradation. The review discusses the physicochemical properties and classification of PEG and its derivatives, the main sites of PEGylation in TPPs, and factors influencing the PEGylation process. It highlights notable cases of PEG-modified TPPs, including antimicrobial peptides (AMPs), interferon, asparaginase, and antibodies, and analyzes the current development status and future prospects of PEGylated TPPs. The review emphasizes the advantages of PEGylation, such as improved solubility, stability, permeability, and pharmacokinetic properties, while also addressing potential drawbacks like reduced bioactivity and limited biodegradability. The study concludes that PEGylation holds significant potential for enhancing the therapeutic applications of TPPs, with ongoing research aiming to optimize PEGylation strategies and explore new approaches to improve drug efficacy and safety.