Fructose is a versatile precursor for food and chemicals. Currently, catalytic production of fructose is achieved by enzymatic isomerization of glucose from renewable lignocellulose. Although the catalyst, glucose isomerase, is selective, it is not stable. Here, aluminum‐containing metal‐organic frameworks (Al‐MOFs) are shown to be active, selective, stable, and reusable for glucose isomerization in ethanol. Al‐MOFs achieved 64% fructose selectivity with 82% glucose conversion at 120 °C, superior performance compared with most other solid catalysts. The amino groups in Al‐MOFs enhance Lewis acid strength, which is responsible for the high fructose selectivity at high glucose conversion. Moreover, the Al‐MOF catalyst is stable and reusable at least four times without losing either activity or fructose selectivity. These findings illustrate compelling opportunities for Al‐MOFs in fructose production and other organic reactions, such as fructose conversion to 5‐hydroxymethylfurfural and levulinic acid.