Current work was performed to evaluate antioxidant activity, α-glucosidase inhibition, phytochemical profiling and in vivo hypoglycemic activity of freeze dried, ultrasonicated Hyophorbe indica leaf extracts. The highest total phenolic contents of 208.77±2.11 mg GAE/g DE and total flavonoid contents of 173.90±2.30 mg Rutin/g DE were obtained in 60% ethanol extract. The 60% ethanol extract exhibited maximum DPPH radical scavenging with IC50 value of 35.35±0.189μg/mL and total antioxidant power of 330.26±3.13 (ASE/g PE), respectively. The highest α-glucosidase inhibition (IC50 36.52 ± 0.08μg/mL) was also observed for 60% ethanol extract. The 60% ethanol extract at dose of 450 mg/kg body weight reduced blood glucose level of alloxan induced diabetic mice by 51.41% which was quite comparable with metformin (56.67%). Twelve compounds namely citric acid, procyanidin B3, epicatechin, procyanidin B2, catechin, catechin derivative, procyanidin B1, apigenin-c-hexocide-c-hexocide, kaempferol, kaempferol derivative, quinic acid derivative and gallic acid have been identified by using UHPLC-Q-TOF-MS/MS in 60% ethanol extract.