Gut microbiota (GM)-derived metabolites play a crucial regulatory role in the occurrence and development of colon cancer. These metabolites, including short-chain fatty acids, bile acid metabolites, nitrogen-containing compounds, and genotoxic substances, can influence colon cancer progression through multiple mechanisms, such as modulation of intestinal barrier function, DNA damage and repair, inflammatory responses, and immune regulation. Dietary patterns can make a difference in colon cancer risk by altering gut microbiota composition and metabolic activity. In recent years, diagnostic and therapeutic strategies based on GM-derived metabolites, including targeted metabolite interventions, personalized nutritional interventions, and microecological regulation, have promised broad clinical applications. This review summarizes the classification and sources of GM-derived metabolites, explores their mechanisms of action in colon cancer, and focuses on the role of the “diet-gut microbiota-metabolite” axis in colon cancer development. In addition, it highlights the clinical translational potential of GM-derived metabolites and current challenges.