In the present scenario, the rate of fossil fuel consumption is very high and increasing rapidly which lead to a further increase in air pollution levels. Due to an increase in pollution level, researchers are striving to discover some cleaner and environment-friendly fuels for the diesel engines. This study was focused on the optimization of the input parameters of the diesel engine running on pongamia biodiesel for improvement in the engine performance. The input parameters selected for optimization were fuel injection pressure, fuel injection timing, pongamia biodiesel blends, and engine load with respect to BTE, BSFC, exhaust gas temperature, and P-max. An experimental analysis was performed according to the response surface methodology technique. The best engine input parameters setting for getting optimum performance was found at fuel injection timing 25 bTDC, fuel injection pressure 226 bar, 40% of pongamia biodiesel blending, at 74% of maximum rated engine load. Experimental and optimized results of the output responses at optimum input parameters were compared and found in the suggested error range.