Naturally replenished biodiesel fuels are more precise in place of diesel engine applications as they have complying thermal properties, which are extensively used by various researchers. However, there is necessity to optimize their utility to meet stringent emission norms as per Bharat Stage VI (BS VI) and Euro 6. From the exhaustive survey on the studies, number of piston grooves (NG), number of grooves-n-bridges on cylinder head (Gr-Br), and inlet valve masking (IVM) using the response surface methodologies (RSM) technique have not been reported on the competence, emissions, and combustion attributes of diesel engines running on Honge oil methyl ester (HOME), hence this is an identified gap in literature. The present simulation work is for optimizing the performance and lessoning exhaust emitted from the diesel prime mover tested on non-conventional and petro fuels. Experimentation was carried out to inquest the competence, combustion, and emittance of a vertical cylinder, overhead valve, water cooling, open or induction swirl diesel engine running on HOME as the injecting fuel. The object of the present effort is to optimize competence of diesel engines via a statistics inquest called designs of experiments (DoE). To curtail the diverse variations to be experimented on, full factorial designs (FFDs) array was employed. The response surface methodologies (RSM)-based nonlinear or quadratic predictors establish the relation between the input parameters and proposed attributes. The RSM-based mathematical predictors are established to prognosticate the distinguished engine output attributes at 95% confidence interval. The response surface assay discovered that a combination of 2B 3G, ‘IVM’ of 900, and ‘NG’ of six grooves yields highest brake thermal efficiency (BTE), lessoning smoke, carbon monoxide (CO), and hydrocarbon (HC), but nitrogenous oxides (NOx) emissions increased slightly. Additionally, combustion attributes, such as Ignition delay (ID) and combustion duration (CD), were lessoned, but peak pressure (PP) and heat release rate (HRR) had a higher contrast to performance of HOME biodiesel in a conventional CI engine.