Emerging evidence from laboratory researches has highlighted the bioactivity of food melanoidins and melanoproteins. Whilst such studies have been carried out with different in vitro systems, information about melanoidins absorption and bio-availability are scarce. However, they are generally considered as poorly absorbable and bio-available compounds. Therefore, we present a review in which the gastro-intestinal tract is hypothesized to be the main site of action of food melanoidins and melanoproteins biological activity. We described recent data supporting this hypothesis both in vitro model systems and in vivo. Importantly, we focused this review only on the effect of melanoidins and melanoproteins extracted from food. Most of the studies had been carried out using water-soluble carbohydrate-based melanoidins isolated from different food sources (beer, barley coffee, coffee). In bakery products, melanoidins are protein-based structure (melanoproteins) which are largely insoluble in water. Dietary melanoidins and melanoproteins have been demonstrated to exert in vitro antioxidant and metal chelating ability in the gastro-intestinal tract reducing the formation of lipid hydroperoxides and advanced lipid oxidation end products during the digestion of meat. The reduction in the formation of these pro-atherogenic compounds has been shown to be followed by a decrease in their absorption in human volunteers. Food melanoidins have also shown in vitro anti-caries and prebiotic activities. We conclude by underlining the possible role of food melanoidins in the prevention of gastro-intestinal tract cancers. We hope this review will stimulate further research on food melanoidins and their biological activities in the gastro-intestinal tract.