There were significant differences between chemical characteristics of ribose (Rib)-, glucose (Glc)-, and fructose (Fru)-lysine (Lys) Maillard reaction products (MRPs). Rib was the most reactive sugar and exerted the greatest change in Maillard-reaction (MR), followed by Glc and Fru in the sugar-Lys model. All three sugar-Lys MRPs not only exhibited strong free radical scavenging activity in chemical systems, but also protected intestinal Caco-2 cells from injury caused by oxidants and transition metal ions. Different chemical characteristics of MRPs generated by the three sugars could not be associated with distinct antioxidant properties in most cases. While antioxidant activities were apparent for whole MRP mixtures, ethanol precipitates (i.e., HMW fraction), more so than ethanol extracts (i.e., LMW fraction), were mainly responsible for scavenging HO and DPPH radicals and protecting against both ferrous ion- and cupric ion- induced cytotoxicity. Free radical scavenging activities of MRPs were influenced not only by high and low molecular fractions, but also by the source of ROS present in the reaction environment.