One of the aromatic contaminants in the oil and fuel is indole, which is toxic even at low doses and is considered as air and water pollutant. In this research, the surface of Zeolite 4A (Z4A) was modified by Cu(II)nanoparticles to introduce a desirable nanocomposite (Cu(II)/Z4A) for indole oxidative degradation. Catalysts characterization was carried out by XRD, SEM, EDS, FTIR, and BET/BJH techniques. Response Surface Methodology (RSM) based on Box-Behnken Design (BBD) was employed for studying several effective factors influences in indole oxidation process, including pH, weight percentage of loaded copper (Cu(wt %)), mass of composite, and indole initial concentration (IND concentration). The obtained results by BBD revealed the solution pH was the most pivotal factor in indole oxidative degradation and predicted that under the optimum experimental conditions, the efficiency should be 98.91%. Moreover, GC-mass analysis was applied for evaluating side products, of which results led to some mechanisms and new productions to be found by using indole oxidative degradation. The results also demonstrated that due to indole oxidation and applying the proper solvent (ethanol), some side products were generated capable of acting as a fuel octane number enhancer, which may play a significant role in obtaining more valuable fuels.