Background: Arum hygrophilum is a traditional medicinal plant indigenous to Jordan. The present study explores its phytochemistry, antioxidative, antidiabesity, and antiproliferative potentialities. Materials and Methods: Column chromatography and HPLC-MS analysis were used for its phytochemical evaluation. Using leaf crude water and ethanol extracts, the antioxidative capacities, their modulation of pancreatic beta-cell proliferation, and insulin secretion as well as glucose diffusion and enzymatic bioassays were evaluated. Results: Three flavonoids (luteolin, isoorientin, and vitexin) and beta-sitosterol have been isolated and their structures determined. HPLC-MS analysis of the ethanol extract further revealed the presence of caffeic, ferulic, gallic, and rosmarinic acids and quercetine-3-O-rhamnoside. The ethanol extract exhibited DPPH and ABTS radical scavenging and antioxidative capacities. A. hygrophilum (1), vitexin (2), and rosmarinic acid (3) inhibited pancreatic lipase (PL) dose dependently with PL-IC50 (mu g/ mL) values in an ascending order: (3); 51.28 +/- 7.55 < (2); 260.9 +/- 21.1 < (1); 1720 +/- 10. Comparable to GLP-1-enhanced beta-cell proliferation in 2-day treatment wells, a dose-dependent augmentation of BrdU incorporation was obtained with the A. hygrophilum aqueous extract (AE) (0.5 and 1 mg/ mL, with respective 1.33-and 1.41-folds, P < 0.001). A. hygrophilum AE was identified as an inhibitor of alpha-amylase/alpha-glucosidase with IC50 value of 30.5 +/- 2.1 mg/mL but lacked antiproliferative effects in colorectal cancer cell lines (HT29, HCT116, and SW620) and insulinotropic effects in beta-cell line MIN6. Conclusion: A. hygrophilum extracts inhibited gastrointestinal enzymes involved in carbohydrate and lipid digestion and absorption.