Background: Hyphaene thebaica L. Mart. (Doum-palm), rich in total phenolics content, is known for its medicinal value in the treatment of several health conditions, such as hypertension, and diabetes mellitus. Aim of the Study: To investigate the hypoglycaemic activity of the dichloromethane, ethyl acetate, and aqueous fractions from doum palm leaves. Then, to characterize the metabolic profile of the most active fraction by LC-HR-MS/MS analysis to detect the responsible metabolites for this activity. Material and Methods: The present study examined the in vitro inhibitory effect of the extract fractions from Doum Palm Leaves at concentrations ranging from 7.81 to 1000.00 μg/ml on α-glucosidase activity, an enzyme responsible for carbohydrate-hydrolysis to monosaccharides and intestinal glucose absorption. Metabolic profiling for the dichloromethane fraction was obtained with LC-HR-MS/MS. Results: The dichloromethane (DCM) fraction inhibited α-glucosidase activity in vitro with an IC₅₀ of 52.40 μg/ml. Twenty-three compounds were identified in the DCM fraction by LC-HR-MS/MS analysis. Most of them were reported for their potential antidiabetic activity. Nevertheless, the III-DCM subfraction (IC₅₀ 3.79 ± 0.17 μg/ml) and the IV-DCM subfraction (IC₅₀ 5.13 ± 0.24 μg/ml) had the best inhibitory activity against α-glucosidase compared with acarbose (IC₅₀ 2.33 ± 0.11 μg/ml).  Conclusions: The results support the use of these fractions obtained from Doum palm leaves to effectively inhibit a crucial enzyme linked to type 2 diabetes and suppress carbohydrate absorption from intestine, and thereby reducing the postprandial increase of blood glucose