Abstract: In biologics, polysorbates (PS 20 and PS 80) are used as surfactants to effectively prevent protein aggregation and maintain protein stability. However, these surfactants can degrade during storage and use, producing free fatty acids and peroxides. These degradation products can chemically react with proteins, leading to protein aggregation and potentially inducing immunogenicity. This review summarized the degradation mechanisms of polysorbates, factors influencing degradation, the impact of degradation on protein stability, and methods for detecting degradation products. Future research directions and challenges are also discussed.