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Pancreatic lipase enzyme plays an important role in fat digestion. This enzyme hydrolyzes fat into fatty acids and glycerol to be absorbed by the body. However, excessive fat intake can cause obesity. Previous studies had shown that papaya seed extract contains flavonoids and was capable of inhibiting pancreatic lipase. However the type and structure of flavonoids contained in the papaya seeds have not been idenfied. The purposes of this study were to isolate papaya seed flavonoids, to identify their structure, and to determine their inhibitory power against pancreatic lipase both in vitro and in silico. This is a descriptive laboratories research conducted in five stages, namely 1) the preparation of papaya seed powder; (2) extraction, isolation, and phytochemical analysis of flavonoids, (3) identification and structure determination of flavonoid isolates using UV-Vis, FTIR and LC-MS/MS specroscopies, 4) in vitro analysis of the inhibition power of flavonoid isolates against pancreatic lipase; and (5) in silico analysis by docking technique using flavonoid isolates as ligands and pancreatic lipases as receptors. This research was able to isolate some of the flavonoid compounds from ethanol extracts of papaya seeds in which all of them have a higher inhibitory power against pancreatic lipase compared to commercial anti-obesity drugs Orlistat. Flavonoid isolate of papaya seed having the highest inhibitory power (53 times the inhibitory power of Orlistat) is liquiritigenin. In silico analysis shows that liquiritigenin has a binding position to the pancreatic lipase enzyme which is relatively the same as Orlistat, but its binding affinity is greater than Orlistat.