The antioxidant activities of different extract of aerial parts of Melothria heterophylla ( Lour.) Cogn, which are broadly used in the Indian indigenous system of medicine for different purposes, has been analyzed. The antioxidant potential of ethyl acetate (EAMH), ethanol (EEMH) along with aqueous (AEMH) fractions were measured applying different antioxidant models, namely determination of total amount of polyphenolics compounds, DPPH (1,1- diphenyl-2-picrylhydrazyl) radical scavenging, nitric oxide scavenging, superoxide anion radical scavenging and hydroxyl radical scavenging assay. It has been found that ethyl acetate fraction possess the maximum amount of polyphenolic compounds (222.71 ± 4.61ìg/mg pyrocatechol equivalent). High Performance Thin Layer Chromatographic (HPTLC) screening shows the presence of phenolic compounds in the ethanol extract. Higher activity was observed in the ethyl acetate fraction in all the above assays followed by ethanol and aqueous extract. The higher activity may be due to presence of richest amount of polyphenolics and flavonoids in it.