Melatonin, a hormone produced by the pineal gland, plays a significant role in inhibiting the epithelial-to-mesenchymal transition (EMT) in cancer. The EMT is a process that contributes to cancer progression by enabling cancer cells to acquire mesenchymal characteristics, increasing invasiveness, and promoting metastasis. Melatonin regulates EMT by modulating key transcription factors, microRNAs, and signaling pathways involved in the process. It has been shown to inhibit the EMT by repressing the expression of EMT-related transcription factors such as Snail, Slug, ZEB1, ZEB2, and Twist1, while upregulating mesenchymal markers. Additionally, melatonin can enhance the expression of microRNAs that suppress EMT-related factors, such as miR-29, miR-30a, miR-34a, miR-200b, and miR-200. Melatonin also inhibits the activation of signaling pathways such as TGF-β, Wnt/β-catenin, Notch, IL6/STAT3, PI3/AKT, and Hedgehog-GLI, which are involved in EMT. These actions of melatonin contribute to its antitumor effects by reducing cancer cell proliferation, invasion, and metastasis. Melatonin is a promising candidate for use as an adjuvant in cancer therapy due to its ability to inhibit EMT, reduce drug resistance, and improve the efficacy of conventional treatments.Melatonin, a hormone produced by the pineal gland, plays a significant role in inhibiting the epithelial-to-mesenchymal transition (EMT) in cancer. The EMT is a process that contributes to cancer progression by enabling cancer cells to acquire mesenchymal characteristics, increasing invasiveness, and promoting metastasis. Melatonin regulates EMT by modulating key transcription factors, microRNAs, and signaling pathways involved in the process. It has been shown to inhibit the EMT by repressing the expression of EMT-related transcription factors such as Snail, Slug, ZEB1, ZEB2, and Twist1, while upregulating mesenchymal markers. Additionally, melatonin can enhance the expression of microRNAs that suppress EMT-related factors, such as miR-29, miR-30a, miR-34a, miR-200b, and miR-200. Melatonin also inhibits the activation of signaling pathways such as TGF-β, Wnt/β-catenin, Notch, IL6/STAT3, PI3/AKT, and Hedgehog-GLI, which are involved in EMT. These actions of melatonin contribute to its antitumor effects by reducing cancer cell proliferation, invasion, and metastasis. Melatonin is a promising candidate for use as an adjuvant in cancer therapy due to its ability to inhibit EMT, reduce drug resistance, and improve the efficacy of conventional treatments.