With the global cancer incidence rate increasing yearly, chemotherapy-induced gastrointestinal mucosal injury has become a crucial factor affecting patients' therapeutic prognosis. There is a lack of effective therapeutic drugs to address this issue. Therefore, it’s urgent to establish more ideal animal models of chemotherapy-induced gastrointestinal mucosal injury to explore its pathogenesis for developing therapeutic drugs. This review seeks relevant literature published between 2019 and 2024, providing a comprehensive summary and analysis from several perspectives, including the selection of experimental animals, chemotherapeutic drugs and modeling methods, evaluation indicators, and practical applications. Furthermore, it highlights several existing issues within current models: the lack of standardized modeling methods, insufficient research on models with a tumor background, and inadequate exploration of novel cell death mechanisms. Additionally, the collation of the literature revealed that traditional Chinese medicine (TCM) is gradually emerging as a research hotspot. TCM has shown potential in the treatment of gastrointestinal mucosal injury. In the future, further exploration of effective medicine is warranted to intervention strategies for chemotherapy-induced gastrointestinal mucosal injury.