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The main side effects associated with continuous infusion of 5-fluorouracil (5-FU) are mucositis, vomiting, nausea, and diarrhea. Dietary factors play a critical role in colorectal cancer management and have gained attention as alternative strategies for cancer prevention. Evidence from preclinical and human studies suggests that polyphenols exert anti-colon cancer activity. However, the mechanisms underlying these effects remain poorly understood. This review highlights the potential of polyphenol-rich foods in the prevention of colorectal cancer, particularly regarding molecular aspects that may provide a plausible means for the prevention of colorectal cancer. 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