Biodiesel is a seemingly suitable alternative substitute for conventional fossil fuels to run a diesel engine. In the first part of the study, the production of biodiesel by modified direct transesterification (MDT) is reported. An enhancement in the biodiesel yield with a considerable reduction in reaction time with the MDT method was observed. The required duration for diesel and biodiesel blending was minimized including glycerol separation time from biodiesel in the MDT method. The development in the automotive sector mainly focuses on the design of an efficient, economical, and low emission greenhouse gas diesel engine. In the current experimental work Ceiba pentandra/Nigella sativa and diesel blends (CPB10 and NSB10) were used to run the diesel engine. A variety of approaches were implemented to improve the engine performance for these combinations of fuels. The fuel injector opening pressure (IOP) was set at 240 bar, the torriodal re-entrant combustion chamber (TRCC) having a six-hole injector with a 0.2 mm orifice diameter each, provided better brake thermal efficiency (BTE) with lower emissions compared with the hemispherical combustion chamber (HCC) and trapezoidal combustion chamber (TCC) for both CPB10 and NSB10. CPB10 showed better performance compared with NSB10. A maximum BTE of 29.1% and 28.6% were achieved with CPB10 and NSB10, respectively, at all optimized conditions. Diesel engine operation with CPB10 and NSB10 at 23° bTDC fuel injection timing, and 240 bar IOP with TRCC can yield better results, close to a diesel run engine at 23° bTDC fuel injection timing, and 205 bar IOP with HCC.