We report a rational design of CaHPO4-alpha-aamylase hybrid nanobiocatalytic system based on allosteric effect and an explanation of the increase in catalytic activity when certain enzymes are immobilized in specific nanomaterials. Employing a calcification approach in aqueous solutions, we acquired such new nanobiocatalytic systems with three different morphologies, i.e., nanoflowers, nanoplates, and parallel hexahedrons. Through studying enzymatic performance of these systems and free alpha-amylase with/without Ca2+, we demonstrated how two factors, allosteric regulation and morphology of the as-synthesized nanostructures, predominantly influence enzymatic activity. Benefiting from both the allosteric modulation and its hierarchical structure, CaHPO4-alpha-amylase hybrid nanoflowers exhibited dramatically enhanced enzymatic activity. As a bonus, the new system we devised was found to enjoy higher stability and durability than free alpha-amylase plus Ca2+.