Fossil fuel engine emissions are a well-known environmental and health hazard. The present study explores a novel approach to mitigating emissions by blending pentanol and biodiesel produced from Neem seed oil with pure diesel to address this issue. The blend consists of 70% pure diesel and 30% biodiesel/pentanol, with pentanol concentrations ranging from 3-12% by volume. The resulting mixtures are labelled according to their biodiesel and pentanol content (B27P3, B24P6, B21P9, and B18P12). To determine the optimal blend, a simplex-lattice design optimization is performed. The results indicate that the blend containing 25.39 vol.% neem seed oil biodiesel and 4.61 vol.% pentanol demonstrates the best engine emission properties. Moreover, the study shows that adding pentanol to the diesel-neem seed oil biodiesel blend significantly improves engine performance. Therefore, the results suggest that diesel-biodiesel-alcohol blends hold promise as a potential alternative fuel source.