Background: Xanthine oxidase (XO) enzyme is directly associated with pathogenesis of gout and indirectly with cancer, diabetes and metabolic syndromes. Allopurinol is a xanthine oxidase inhibitor which is useful in the treatment of gout but it causes side effects in humans and birds. Therefore, this study sought to identify the alternative compound from the natural resources with fewer side effects than the conventional ones. Objectives: The present study was designed to find out the xanthine oxidase inhibitory activity of Piper betle phytocompounds in comparison with Allopurinol. Methods: The detection of phytocompounds present in the P. betle L. extract was identified through Gas Chromatography Mass Spectrometry (GC-MS) analysis. The insilico analysis and ADMET properties were evaluated for the GC-MS derived P. betle phytocompounds. Among the 32 phyto compounds of P. betle, 18 were showed favourable affinity with xanthine oxidase and their different conformational structures were docked in schrodinger module with xanthine oxidase enzyme structure. The interpretation of results was carried out through GLIDE XP Scoring, GLIDE Energy, MM-GBSA energy and hydrogen bond and PiPi interactions. Further the absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis were also carried out using QIKPRO programme. Results: The results revealed that, the twelve phytocompounds of P. betle showed GLIDE XP docking score (- 6.881 to - 4.766 Kcal/mol) higher than allopurinol (- 4.535 Kcal/mol) and 11 phytocompounds showed higher GLIDE energy (- 42.822 Kcal/mol to - 36.706 Kcal/mol) than allopurinol (- 32.676 Kcal/mol). Chromonol and eugenol were the most potential compounds of P. betle which showed both hydrogen bond and Pi-Pi interactions with the target xanthine oxidase as that of standard drug allopurinol. The selected phytocompounds satisfied the ADME descriptors and have no violation of Lipinski's rule of five. Conclusions: The insilico and ADMET profile study on the phytocompounds of P. betle predicted their promising potential xanthine oxidase inhibition activity and they could be developed as alternate molecules against synthetic agents by invivo experiments for the treatment of xanthine oxidase associated diseases like hyperuricimia and cardiovascular disorders.