Eighteen dihydroindolizino[8,7-b]indole derivatives 4a–r were designed, synthesized and evaluated as new α-glucosidase inhibitors. These derivatives were synthesized by an efficient one-pot two-step reaction under mild condition. All the synthesized compounds were found to be more active than the standard drug acarbose (IC₅₀ = 750.0 ± 1.5 µM) with IC₅₀ values in the range of 107.2 ± 1.0–275.4 ± 1.5 µM. Among the synthesized compounds, diethyl derivative 4o and dimethyl derivative 4 h exhibited the highest anti-α-glucosidase activities (IC₅₀ = 107.2 ± 1.0 and 118.0 ± 0.7 µM, respectively). Kinetic analysis of the compound 4o revealed that this compound is a competitive inhibitor for α-glucosidase with K_i value of 113 µM. Furthermore, the docking study on the compounds 4o and 4 h revealed that these compounds interacted with the important residues in the active site of the homology model of α-glucosidase.