Dioscorea bulbifera is commonly known as Aerial Yam is a perennial, non-spiny, climbing plant consist of numerous medicinal benefits. It contains a large number of polyphenols including organic acids and saponins. Aim of the present study is to screen the anti-inflammatory activity of saponin from the aqueous methanol fruit extract of Dioscorea bulbifera. The presence of saponin was tested using the qualitative phytochemical screening and separated using TLC. Total saponin content was 30µg/g. The identification of saponin activity against inflammation was carried out using several assays such as Cyclooxygenase inhibition assay, Lipooxygenase Inhibition assay and Protein denaturation inhibition assay using Diclofenac sodium. In silico study was conducted for the evaluation of anti-inflammatory activity using the COX-2 as target. The docking results revealed that dioscin was predicted to have the highest binding efficacy with COX-2 receptor with a binding energy of -662.07 kcal/mol. Thus the study shows that the Dioscorea bulbifera fruit contain a safe and effective Anti-inflammatory activity.