Colorectal cancer, a chronic gut disease, is the second most deadly cancer worldwide, causing 1 million deaths/year. To the best of our knowledge, there are no data on coffee melanoidin's colonic metabolite effect on colon cancer cell events associated with the disease's pathophysiology, such as elevated Reactive Oxygen Species (ROS) levels and cell proliferation, linked with the former biological event. Short-chain fatty acids (SCFAs) and phenolic antioxidants are released during coffee melanoidin fermentation. Coffee melanoidins were isolated from Arabica Brazil roasted coffee beans and were fermented under simulated colonic human conditions for 48 hours employing Simgi® (Dynamic Gastrointestinal Simulator). The effect of coffee melanoidin fermentation metabolites on ROS production and cell proliferation was studied in Caco-2 human colon cancer cells. Intracellular ROS production was evaluated using an oxidant-sensing probe, 2´,7´-dichlorodihydrofluorescein diacetate (DCFH-DA). The colony formation assay was used to determine potential changes in cell proliferation. Colonic metabolites (100 µg/ml) caused a statistically significant (p<0.05) decrease in intracellular basal ROS production and a suppression in colon cancer cells proliferation (83%, 48 hours), compared with the control (without treatment), in a time-dependent manner in cell proliferation. Therefore, these preliminary results suggested that coffee melanoidin colonic metabolites might limit colon cancer development. The metabolites produced, short-chain fatty acids and phenolic compounds, among others, may synergistically contribute to the observed effect.