A new series of quinoline derivatives 6-30 was identified as potent α-glucosidase inhibitors. These analogs exhibited inhibitory potentials (IC50 values) in the ranges between 2.60 to 102.12 μM. Among the series, compounds 24 (2.60 ± 0.01 μM), 27 (2.60 ± 0.01 μM) and 20 (2.86 ± 0.01 μM) were found exceptionally potent (> 14 times ~ than the standard) inhibitors of α-glucosidase when compared to the standard acarbose (IC50 = 38.25 ± 0.12 μM). Molecular docking studies on two most active compounds 24 and 27 corroborated that compound 24 adopted linear position to optimally fit into the binding site of α-glucosidase. Observations for the best position of compound 24 showed a total of four interactions towards catalytically active site residues of α-glucosidase involving amino acid residues such as Phe-177 and Asp-214. Oxadiazole ring of compound 24 interacted with His-279. Compound 27 formed one hydrogen bonded interaction (N-methylacetamide) and three arene-arene interactions (quinoline and 1,3,4-oxadiazole moiety). Quinoline moiety of compound 27 formed two π-interactions with Phe-157. All compounds were tested for cytotoxicity but none of them found to be cytotoxic.