The size and defects of crystalline inorganic materials are crucial in many applications, especially in catalysis, as they often lead to enhanced/emerging performance. So far, the application of modulation chemistry strategies has not been able to provide high-quality functional metal organic framework (MOF) nanocrystals that minimize size while maximizing defects. We report here a universal sustainable strategy for designing highly defective and ultra small tetravalent MOF (Zr, Hf) crystals (approximately 35% missing linkers, 4-6 nm). Advanced characterization has been conducted to elucidate the main factors controlling the crystallization mechanism and determine the properties of defects. Ultra small nano MOFs exhibit excellent performance in peptide hydrolysis reactions, including high reactivity, selectivity, diffusion, stability, and emerging customizable reactivity and selectivity for peptide bond formation by simply changing the reaction solvent. Therefore, these highly defective ultra small M (IV) - MOFs particles have opened up new prospects for the development of multiphase MOF catalysts with dual functions.