Cancer remains a leading cause of mortality worldwide. Chemotherapy serves as a cornerstone of cancer treatment, providing significant benefits in tumor control and survival. However, its therapeutic efficacy is often compromised by gastrointestinal toxicity, which impairs quality of life and may necessitate treatment modifications. Disruption of the gut microbiota has been recognized as a key factor in the development of these toxicities.This review synthesizes evidence on how chemotherapeutic agents disrupt gut microbial balance and exacerbate gastrointestinal toxicity through epithelial barrier damage, inflammatory activation, and metabolic disturbance. It also examines diverse interventions, including dietary modifications, probiotics, prebiotics, synbiotics, traditional herbal medicines, and fecal microbiota transplantation, that aim to restore microbial homeostasis and reduce gastrointestinal injury.This review provides a symptom-oriented framework linking specific clinical manifestations of chemotherapy-related gastrointestinal toxicity with underlying microbial alterations. It further integrates emerging evidence across nutritional, microbial, and herbal approaches, emphasizing shared therapeutic pathways and highlighting prospects for personalized microbiota-based strategies to improve treatment tolerance and patient outcomes.© 2025 S. Karger AG, Basel.