The paper presents methods to determine the optimum input parameters of CNG addition, biodiesel blend ratio, and engine speed to improve engine responses in terms of exhaust emissions, vibration, and noise of CNG-biodiesel-diesel fuelled engine. Box-Behnken based on response surface methodology was used to predict and optimise input parameters. Variance analysis was applied to determine the significant relationship between the input parameters and engine responses. At optimum input parameters (CNG addition=9.24 L/min, biodiesel blend ratio=40%, engine speed=1524.24 rpm), the optimum engine responses of NOx, CO, CO2, O2, engine vibration acceleration, and noise were 93.77 ppm, 438.05 ppm, 1.47%, 18.59%, 37.17 m/s2 and 91.34 dB[A], respectively. In terms of coefficient determination of R2, the values were 99.11%, 99.22%, 99.41%, 99.70%, 98.65%, and 98.60% respectively. The correlation between the optimised result and the engine test result showed an acceptable error limit for NOx, CO, CO2, O2, engine vibration acceleration, and noise as 4.2%, 3.8%, 4.9%, 0.25%, 4.12%, and 0.17%, respectively.