Background: Obesity is a disorder of lipid metabolism and the enzyme involved in this process could be selectively targeted to develop anti obesity drugs. Inhibition of digestive enzymes is one of the most widely studies mechanisms used to determine the hypolipidemic and hypoglycemic agent of natural products for anti-obesity agent screening. Aims: To evaluate the inhibitory potential of G. mangostana extract, xanthone and α-mangosteen compound toward pancreatic lipase and α-amylase enzyme as once of anti-obesity mechanism. Material and Methods: The IC50 value of the mangosteen pericarp extract, xanthone, and α-mangosteen toward pancreatic lipase and α-amylase were determined in vitro compared to orlistat and acarbose as standard drugs. Results: Mangosteen pericarp extract contains phenol, terpenoid, saponin, flavonoid and tannin. Mangosteen pericarp extract is a more active compound in inhibiting the PPL activity compared to α-mangosteen, and xanthone. Mangosteen pericarp extract shows the higher activity compared to xanthone but still lower activity compared to α-mangosteen. However, its activity is still lower than standard drugs. Conclusions: Our in vitro, confirmed that the mangosteen pericarp extract has the phytochemical bioactive content that possesses anti-obesity potential through pancreatic lipase and α-amylase inhibitory activity.