The increment in the usage of automobiles is resulting in increased greenhouse gases (GHG) emissions continuously and there is a substantial need to reduce them effectively. The present research work investigates the emission behavior of waste cooking oil biodiesel doped with CuO nanoparticles during testing in Compression Ignition (CI) engines. This investigation is based on the effective emission reduction analysis emitted by diesel fuel during experimentation on CI engines. It suggests a cost effective modification of biodiesel as a fuel prepared from waste cooking oil (WCO) by a novel hydrodynamic cavitation technique which includes the hydrodynamic cavitation reaction mixture composed of 1.28 L of methanol and 10 g KOH and 5 L of preheated WCO at 45 °C in the cavitation reactor for 40 min. These reactants are synthesized utilizing the principle of cavitation and the final manufactured esterified oil is authenticated with ASTM Standard property measurement for suitability check. In the research work, two different investigations are carried out. In the first one, WCO biodiesel-diesel blends of 0, 30, and 100% (B0, B30, B100) ratio are prepared and the emission characteristics have investigated at 1500 rpm constant speed with varying load and indicated mean effective pressure (IMEP). In the second investigation, the emission suitable blend B30 is doped with CuO nanoparticles, keeping other parameters as per the previous setup, the emission characteristics investigated for the second one. For precise results, more experimental trials are needed to achieve this decrease in the emission of harmful gases. Using an amalgamation of L9 Taguchi and response surface methodology (RSM) the maximum emission control with a minimum number of experimental trials is achieved. The first investigation includes the predefined predictors as A (blend), B (load), and C (IMEP), where blends (0 ≤ A ≤ 100%), load (0 ≤ B ≤ 12 kg), IMEP (3.5 ≤ C ≤ 7.5 bar) are controllable features. Optimization process resulted into a minimum emission of CO, CO2, and NOx by appertaining the condemnatory merger of inputs such as blend B0 (Diesel), load 12 kg, and IMEP 3.48 bar in the first investigation, which has resulted into 0.08 ppm CO, 0.6 ppm CO2 and 30 ppm NOx emission. Taguchi analysis-based second experimental investigation includes the predefined predictors as A (CuO), B (load), and C (IMEP), including nanoparticles CuO in blend B30, and the prognosticated results of optimization are 0.03 ppm CO, 0.3 ppm CO2 and 21 ppm NOx emission. In current investigation, the percentage reduction is found to be 92.3%, 94.82%, and 96% compared to the emission of diesel in CO, CO2 and NOx gases, respectively. The coefficient of determination is almost equal to 1, which reveals the chosen optimization technique is very accurate in prediction. The investigation has provided suitable minimum emission characteristics in a cost-effective way.