A new recyclable catalyst for pyrolysis has been developed by combining calculations and experimental methods. In order to understand the properties of the new cluster designed catalysts, cellulose (a major component of plants) as a biomass model compound was pyrolyzed and catalyzed with different cluster designed catalysts. The NiaFeb (2 ≤ a + b ≤ 6) catalyst clusters structures were calculated by using Gaussian and Materials Studio software to determine the relationships between catalyst structure and bio-oil components, which is essential to design cluster designed catalysts that can improve bio-oil quality. GC-MS analysis of the bio-oil was used to measure the effects on the different catalyst interactions with cellulose. It was found that the NiFe cluster designed catalysts can increase the yield of bio-oil from 35.8% ± 0.9% to 41.1% ± 0.6% and change the bio-oil composition without substantially increasing the water content, while substantially decreasing the sugar concentration from 40.1% ± 1.3% to 27.5% ± 0.9% and also producing a small amount of hydrocarbon compounds. The catalyst with a high Ni ratio also had high Gibbs free energy, ΔG, likely also influencing the decrease of sugar and acid while increasing the ketone concentrations. These results indicate the theoretical calculations can enhance the design next-generation cluster designed catalysts to improve bio-oil composition based upon experiments.