In this study, we have investigated the potential of two classes of thioglucoside analogues of gliflozins as antidiabetic drugs, one with substitutions of S-atoms in meta-positions (similar to C -glucoside SGLT2 inhibitors, TAGs A , B , and C ) and the other with substitutions of S-atoms in ortho-positions (similar to O -glucoside SGLT2 inhibitors, TAGs D , E , F , and G ). These TAGs were confirmed to show good stability against β-glucosidase and to have no acute toxicity to cultured cells. Most importantly, TAGs D , E , F , and G all showed high inhibitory activity against SGLT2 (IC 50 : 2.0-5.9 nM) and thus have great potential to be developed as new gliflozin drugs. Compared with the synthesis of C -glucoside gliflozins, the synthesis of TAGs is simple, efficient, and associated with low costs, high yields, and very mild reaction conditions.