As antioxidants prevent free radical caused DNA damage, they lower the risk of developing chronic diseases. The present study evaluated the impact of fatty acid-rich fractions of Andrographis Paniculata Nees (AP) on free radical-induced DNA damage. We prepared fatty acid-rich fractions with dried AP plants and analyzed them qualitatively using gas chromatography. In order to determine their cytotoxicity and free radical scavenging activities, MTT and Viacount assays were performed. In vitro proliferation assay was performed to assess the cell proliferation after treating with hydrogen peroxide (H2O2) and Ultra Violet-C (UVC). Further testing of the fractions was carried out using a high alkaline comet assay (pH>13) to determine their DNA-protective capacity. Our results indicated that AP fractions containing fatty acids possess DNA protective ability against H2O2 and UVC rays in human dermal fibroblasts.