A series of 6-chloro-3-oxindole derivatives 1-25 were synthesized in high yields by the reaction of 6-chlorooxindole with different aromatic aldehydes in the presence of piperidine. All the synthesized compounds were isolated with E configuration. The structures were confirmed using spectroscopic techniques, including (1)H NMR and EIMS. These compounds showed varying degree of yeast α-glucosidase inhibition and seven were found as potent inhibitors of the enzyme. Compounds 2, 3, 4, 5, 6, 23, and 25 exhibited IC50 values 2.71±0.007, 11.41±0.005, 37.93±0.002, 15.19±0.004, 24.71±0.007, 17.33±0.001, and 14.2±0.002μM, respectively, as compared to standard acarbose (IC50, 38.25±0.12μM). Docking studies helped to find interactions between the enzyme and the active compounds. As a result of this study, oxindoles have been discovered as a new class of α-glucosidase inhibitors which have not been reported earlier.