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Chemotherapy-induced oral mucositis (CIOM) is a prevalent toxic side effect of cancer treatment, severely compromising patients' quality of life, nutritional intake, and treatment adherence. Its pathogenesis has evolved from the traditional model of simple epithelial damage to a complex pathological process involving the interplay of chemotherapy toxicity, host immunity, and oral microbiota. Research indicates that chemotherapy can disrupt the oral microbiota, promoting the proliferation of pathogenic bacteria and exacerbating damage to the mucosal barrier and local inflammatory responses. Current clinical interventions, such as mouth rinses and cryotherapy, have limited efficacy and lack standardized protocols. In recent years, modulating the oral microbiota has emerged as a promising therapeutic strategy. Probiotic preparations have demonstrated potential in clinical studies to alleviate CIOM severity through mechanisms including competitive colonization, metabolic regulation, and immunomodulation. This review systematically summarizes the clinical manifestations, epidemiological characteristics, pathogenesis, and existing treatment strategies of CIOM. It highlights the critical role of the oral microbiota in CIOM pathogenesis and further outlines the promising application prospects of microbiome-targeted interventions, particularly probiotic preparations, aiming to provide novel insights for CIOM prevention and treatment.