In this study, a novel series of pyrano[3,2-c]quinoline-1,2,3-triazole hybrids 8a-o were synthesized and evaluated against the α-glucosidase enzyme. All compounds showed significant in vitro inhibitory activity (IC50 values of 1.19 ± 0.05 to 20.01 ± 0.02 μM) compared to the standard drug acarbose (IC50 = 750.0 μM). Among them, 2-amino-4-(3-((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile (compound 8k) demonstrated the best inhibitory effect toward α-glucosidase (IC50 = 1.19 ± 0.05 μM) with a competitive pattern of inhibition. Since compound 8k was synthesized as a racemic mixture, molecular docking and dynamics simulations were performed on R- and S-enantiomers of compound 8k. Based on the molecular docking results, both R- and S-enantiomers of compound 8k displayed significant interactions with key residues including catalytic triad (Asp214, Glu276, and Asp349) in the enzyme active site. However, an in silico study indicated that S- and R-enantiomers were inversely located in the enzyme active site. The R-enantiomer formed a more stable complex with a higher binding affinity to the active site of α-glucosidase than that of the S- enantiomer. The benzyl ring in the most stable complex ((R)-compound 8k) was located in the bottom of the binding site and interacted with the enzyme active site, while the pyrano[3,2-c]quinoline moiety occupied the high solvent accessible entrance of the active site. Thus, the synthesized pyrano[3,2-c]quinoline-1,2,3-triazole hybrids seem to be promising scaffolds for the development of novel α-glucosidase inhibitors.