Pomelo is a native citrus fruit of Southeast Asia and a cash crop to Thailand. Pomelo (Citrus grandis (L.) Osbeck) contains of many flavonoids that have shown the beneficial effects on human health. However, studies related to antihyperglycemic, antihyperlipidemic, and antiglycation properties of pomelo flavonoids are limited. The objective of this study was to quantify of flavonoids in the pulp of six pomelo cultivars (Kao Yai, Thong Dee, Kao Tanggwa, Kao Nam Pueng, Tar Koi and Tubtim Siam) and to determine the -glucosidase and pancreatic -amylase inhibitory activities of pomelo extracts. Moreover, the study was to investigate the effect of pomelo extracts on the inhibition of pancreatic lipase and pancreatic cholesterol esterase activities as well as the inhibition of cholesterol micelle formation, and bile acid binding. Finally, the present study sought to characterize the protein glycation inhibitory activity of pomelo extracts in a bovine serum albumin (BSA)/fructose system. The results demonstrated that the pomelo extracts slightly inhibited -glucosidase and pancreatic -amylase. In addition, the pomelo extracts have shown moderate pancreatic lipase and cholesterol esterase inhibitory activities. The pomelo extracts (5 mg/ml) inhibited cholesterol micellization with values 4-15%. Moreover, taurocholic acid, taurodeoxycholic acid, and glycodeoxycholic acid was markedly bound by all pomelo extracts (2 mg/ml) that exhibited binding capacity around 2-20%, 10-20%, and 5-18%, respectively. The results demonstrated that pomelo extracts significantly inhibited the formation of advanced glycation end products (AGEs). Furthermore, they reduced the level of fructosamine, the formation of Nε-(carboxymethyl) lysine (CML), and the level of amyloid cross β -structure. The pomelo extracts also prevented oxidative protein damages, including effects on protein carbonyl formation and thiol oxidation of BSA. The findings could provide a new insight into the naturally occurring antihyperglycemic, antihyperlipidemic, and antiglycation properties of pomelo extracts for development as a nutraceutical food in order to prevent diabetes, hyperlipidemia and its complications.