In this study, an aqueous extract of leaves from Melothria maderaspatana was tested for in vitro antioxidant activity. Free radical scavenging assays, such as hydroxyl radical, hydrogen peroxide, superoxide anion radical and 2,2-diphenyl-1-picryl hydrazyl (DPPH), 2,2'-azinobis-(3-ethyl-enzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, and reducing power assay, were studied. The extract effectively scavenged hydroxyl radical, hydrogen peroxide and superoxide anion radicals. It also scavenged DPPH and ABTS radicals. Furthermore, it was found to have reducing power. All concentrations of leaf extract exhibited free radical scavenging and antioxidant power, and the preventive effects were in a dose-dependent manner. The antioxidant activities of the above were compared to standard antioxidants such as butylated hydroxytoluene (BHT), ascorbic acid, and alpha-tocopherol. The results obtained in the present study indicate that the M. maderaspatana extract could be considered a potential source of natural antioxidant.