Malignant tumors of the digestive system represent a class of diseases characterized by high malignancy, strong metastatic potential, and poor prognosis, with an incidence rate showing a continuous upward trend. Surgery-based comprehensive therapy remains the primary treatment modality. Although the application of emerging therapies such as immunotherapy and targeted therapy in recent years has improved patient survival rates, drug resistance and tolerance remain key bottlenecks limiting therapeutic efficacy. Therefore, exploring new alternative or adjuvant therapeutic strategies is crucial. Melatonin, a hormone secreted by the pineal gland, not only regulates circadian rhythms but also possesses significant anti-inflammatory and antioxidant properties. It also plays an important regulatory role in inhibiting tumorigenesis, development, and metastasis, demonstrating potential as a novel adjuvant anti-tumor agent. This article aims to review the research progress on the mechanisms of action and combined applications of melatonin in digestive system tumors, to provide new insights and theoretical foundation for expanding its clinical application in the treatment of these malignancies.