We report synergetic effects of functionalized mesoporous silica (FMS) and urea to promote favorable protein conformational changes. The specific activity of glucose isomerase (GI) entrapped in FMS in the presence of urea was approximately double that of GI in solution in the absence of urea. Rather than losing all activity in a denaturing solution of 8.0 M urea, the specific activity of GI entrapped in FMS remained higher than the highest specific activity of GI free in solution.