© 2020 Elsevier LtdThe present study was devoted to investigating the effect of input parameters— Mono ethylene glycol supported emulsion (MEGSE) ratio and engine speed—on their corresponding engine-out parameters including engine torque, BSFC, BSEC, BTE, CO, NOx, and soot emissions. At full-load condition, the MEGSE concentrations ranging from 0% to 20% were employed, whereas the engine speed varied from 1800 rpm to 3250 rpm. In comparison with neat diesel fuel, the BTE and engine torque decreased at high levels of MEGSE, and the CO, NOx, and soot emissions declined as well. The BSFC and BSEC values of the MEGSE/diesel blends was higher in comparison with base fuel. The response surface method was employed to propose multi-regression models and predict engine performance and exhaust emissions. Besides, the analysis of variance technique was utilized to analyse the derived models in terms of statistical significance. The optimization was performed to maximize engine performance and minimize exhaust emissions. The optimal engine operating conditions were found to be at an engine speed of 2603 rpm and a MEGSE concentration of 15.6%. The findings indicated that at this optimal condition, the values of engine torque, BTE, BSFC, BSEC, CO, NOX, and soot were found to be 17.24 Nm, 28.52%, 505.7 g/kWh, 9.48 MJ/kWh, 2123 ppm, 368 ppm, and 2.24 m−1, respectively.