We found here that ε4‐carried T2DM patients showed elevated GSK‐3β activity in periphery blood, which was positively correlated with diabetes duration, plasma HbA1c, and FPG level, which provided novel information to link ApoE gene polymorphisms and GSK‐3β with cognitive functions in T2DM patients. This evidence concerns the gene APOE and type 2 diabetes mellitus.