Abstract: OA was linked with 1-Deoxynojirimycin (1-DNJ) at its C-28 through acarbon chain by bromine substitution and nitrogen substitution, five novel oleanolic acid derivatives (OADs) of that were designed and synthesized by the active group combination, which were confirmed by ¹H NMR, ¹³C NMR and HRMS determination. The inhibittion activity of these five OADs on α-glucosidase activity was further evaluated using amicro determination model based on the reaction of α-glucosidase and PNPG, the structure-activity relationship of these OADs was investigated by molecular docking as well. The results showed that all of the five OADs had higher inhibition activity on α-glucosidase than OA, and the OADs with a bridge link which consisted of three methylenes between OA and 1-DNJ group (compound 2b) showed the highest inhibition activity, of which the IC₅₀ was 0.786 mmol/L (IC₅₀ of OA was 2.387 mmol/L). Enzyme inhibition kinetic analysis suggested that these compounds were mixed-type inhibitor of α-glucosidase. The results of molecular docking indicated that hydrogen bond and van der Waals force played critical roles in the combination between the inhibitor and α-glucosidase, the inhibition activities enhanced with the increasing of the number of the hydrogen bonds. Seven hydregon bonds were found in the molecular docking model between the compound 2b and α-glucosidase. The free energy of the binding between compound 2b and α-glucosidase was only -17.19 kJ/mol, which was slightly higher than acarbose. Therefore, the synthesized oleanolic acid-1-DNJ derivative (2b) had a good inhibitory activity against α-glucosidase.