Colorectal cancer (CRC), one of the most prevalent malignant neoplasms, ranks as a leading cause of cancer-related mortality on a global scale. A particularly aggressive variant of CRC is colitis-associated colon cancer (CAC). Patients with chronic inflammatory bowel disease (IBD) are at increased risk for CAC. The pathogenesis of CAC is influenced by numerous factors and is highly complex. Due to the complexity of the mechanism by which chronic inflammation of the intestine leads to the transformation of colorectal cancer, there is currently no standardized strategy for the advance prophylaxis of CAC. Significantly, phyto-derivatives exhibit significant potential in the prevention of CAC. Currently, researches have demonstrated that natural products extracted from plants including polyphenols, alkaloids, saponins, terpenoids, polysaccharides, and plant extracellular vesicles can achieve significant anti-inflammatory, antioxidant, and gut microbiota regulating activities through oral administration. It is a valuable opportunity for the application of natural products in chronic intestinal inflammation to inhibit the transformation of intestinal inflammation into malignancy. In this review, we provide a comprehensive analysis of the predisposing factors and pathogenesis of CAC, along with the mechanisms through which various plant-derived compounds inhibit CAC development. This work aims to provide innovative and practical treatment strategies for the prevention of CAC.