The antioxidant activity of roasted coffee residues was evaluated. Extraction with four solvents (water, methanol, ethanol, and n-hexane) showed that water extracts of roasted coffee residues (WERCR) produced higher yields and gave better protection for lipid peroxidation. WERCR showed a remarkable protective effect on oxidative damage of protein. In addition, WERCR showed scavenging of free radicals as well as the reducing ability and to bind ferrous ions, indicating that WERCR acts as both primary and secondary antioxidants. The HPLC analyses showed that phenolic acids (chlorogenic acid and caffeic acid) and nonphenolic compounds [caffeine, trigonelline, nicotinic acid, and 5-(hydroxymethyl)furfuraldehyde] remained in roasted coffee residues. These compounds showed a protective effect on a liposome model system. The concentrations of flavonoids and polyphenolic compounds in roasted coffee residues were 8,400 and 20,400 ppm, respectively. In addition, the Maillard reaction products (MRPs) remaining in roasted coffee residues were believed to show antioxidant activity. These data indicate that roasted coffee residues have excellent potential for use as a natural antioxidant source because the antioxidant compounds remained in roasted coffee residues.