Hydrogenolysis of C-O bonds is a highly challenging reaction with the most efficient catalysts based on bimetallic assemblies. Systematic studies to identify the optimum metal combination have not been performed and, therefore, we designed a method to screen multi-metallic catalysts, including all water stable transition metals, using diphenyl ether as a model substrate. Bimetallic Pd-Pt (70 : 30) nanoparticles were the most efficient, catalyzing the hydrogenolysis of the C-O bond in diphenyl ether at 95 degrees C and 1 atm of hydrogen in quantitative yield. This research provides insights into the activity of multi-metallic catalysts in hydrogenolysis reactions. The catalyst was successfully applied in the reductive fractionation of bio-mass affording key products in near-quantitative yields.