The current research focuses on the optimization of D+LPO (20% waste-based lemon peel oil and 80% diesel) fueled Common Rail Direct Injection (CRDi) engine fuel injection parameters for the optimum performance and emission characteristics. The foremost influential fuel injection parameters such as Injection Pressure (IP), Dwell Time (DT), Pilot Mass (PM) and Pilot Timing (PT) are considered to enhance the performance and decrease the emissions. Engine output responses like Brake Thermal Efficiency (BTE), Brake Specific Fuel Consumption (BSFC), Hydrocarbons (HC), Carbon monoxide (CO), nitrogen oxides (NOx) and smoke emissions are modeled by using Response Surface Methodology (RSM). Analysis of Variance (ANOVA) disclosed that all the developed models are statistically significant with an R2 value of 0.9735 for BTE, 0.9719 for BSFC, 0.8517 for CO, 0.956 for HC, 0.9282 for NOx and 0.927 for smoke. Multi-objective optimization is performed using the desirability function approach to minimize the BSFC, HC, CO, NOx and smoke with maximum BTE. The D+LPO blend at IP 700 bar, PM 20%, PT 27°bTDC and 12° DT was predicted to be an optimum operating condition for this particular engine. Confirmatory tests were used to validate the predicted combination, and the prediction error was determined to be less than 5%.