α-Glucosidase is the key intestinal enzyme having clinical relevance in the treatment of diabetes mellitus. Therefore, in the present investigation an attempt was made to evaluate the inhibitory effect of medicinal mangrove species Rhizophora apiculata on α-glucosidase.The leaf materials of R. apiculata were extracted with five different solvents viz., toluene, chloroform, ethyl acetate, ethanol, and methanol and their phytochemical constituents were qualitatively analyzed. Different concentrations of extracts (2.5, 10, 40, and 80μg/ml) were used to determine the in vitro α-glucosidase inhibitory action. The enzyme kinetics of effective extract was determined by Lineweaver Burk plot analysis. The metabolites in the effective ethanolic extract of R. apiculata (EtOH-RA) were also fractionated and identified by HPLC–MS. Then, molecular interaction of these metabolites with modeled α-glucosidase was studied using Auto Dock.The quantitative phytochemical studies showed a huge amount of total alkaloids (250.53±0.51mg/g) present in the EtOH-RA which exhibited significant α-glucosidase inhibitory activity compared to other extracts. The dichloromethane and acid aqueous fraction also showed significant inhibition (P<0.01) compared to ascarbase. The enzyme kinetics indicates that EtOH-RA and dichloromethane fraction is an uncompetitive inhibitor. Further, nine different alkaloids were identified in the dichloromethane and acid aqueous fraction of EtOH-RA. Docking studies exhibited more interaction between the alkaloid and α-glucosidase receptor.This study concludes that EtOH-RA and its dichloromethane fraction act as an effective α-glucosidase inhibitor and have a potential in the management of diabetes.