To find potential α-glucosidase inhibitors, indolo[1,2-b]isoquinoline derivatives ( 1 - 20 ) were screened for their α-glucosidase inhibitory effects. All derivatives presented potential α-glucosidase inhibitory effects with IC 50 values of 3.44 ± 0.36~41.24 ± 0.26 μM compared to the positive control acarbose (IC 50 value: 640.57 ± 5.13 μM). In particular, compound 11 displayed the strongest anti-α-glucosidase activity, being ~186 times stronger than acarbose. Kinetic studies found that compounds 9 , 11 , 13 , 18 , and 19 were all reversible mix-type inhibitors. The 3D fluorescence spectra and CD spectra results revealed that the interaction between compounds 9 , 11 , 13 , 18 , and 19 and α-glucosidase changed the conformational changes of α-glucosidase. Molecular docking and molecular dynamics simulation results indicated the interaction between compounds and α-glucosidase. In addition, cell cytotoxicity and drug-like properties of compound 11 were also investigated.