The global incidence rate of cancer is increasing yearly, and chemotherapy-induced gastrointestinal mucosal injury has become a crucial factor affecting patients’ therapeutic prognosis; however, there is currently a lack of effective therapeutic drugs to address this issue. There is thus an urgent need to establish more ideal animal models of chemotherapy-induced gastrointestinal mucosal injury, to support the exploration of its pathogenesis and the development of therapeutic drugs. This review considered relevant literature published during the period from 2019 to 2024, to provide a comprehensive summary and analysis from several perspectives, including the selection of experimental animals, chemotherapeutic drugs and modeling method, evaluation indicators, and practical applications. Furthermore, we highlight several existing issues with current models, including the lack of standardized modeling method, insufficient research on models with a tumor background, and inadequate exploration of novel cell death mechanisms. This collation of the literature also revealed the gradual emergence of traditional Chinese medicine as a research hotspot, with potential for the treatment of gastrointestinal mucosal injury. Further studies of effective medicines are warranted to identify interventional strategies for chemotherapy-induced gastrointestinal mucosal injury.