We report here a new and sustainable route to produce a series of ultra-small UiO-type MOFs (4-6 nm) with exceptionally high defect content. A set of advanced characterization techniques revealed that the large defect content on such small UiO-66 nanoparticles is attributed to the presence of missing linker defects and that the crystallization is growth-dominated. Noteworthy, this strategy is versatile and can be applied to many UiO-66(Zr)-X derivatives (X = NH2, NO2, (OH)2, Br), to the Hf counterpart UiO-66(Hf) and finally to other Zr-MOFs structures like the Zr fumarate MOF-801(Zr), resulting in ultra-small nanoMOFs with very high defect content. Additionally, our mild green synthetic conditions are far more sustainable than the traditional solvothermal routes, which is of interest to save energy and/or strongly reduce the quantity of hazardous wastes. Moreover, the nanoMOFs synthesized here present excellent catalytic performance in peptide bond hydrolysis showing much better reactivity, chemicals diffusion, selectivity and stability than benchmark catalysts. Significantly, these nanoMOFs show bifunctionality as by simply changing the reaction solvent, the hydrolysis of peptide bonds can be replaced by the opposite condensation reaction, resulting in amide bond formation. Additionally, these nanoMOFs also show novel tailorable selectivity due to the molecular-sieving effect.