The exploitation of petroleum derivatives to meet the energy demands of the cutting edge is thought of as impractical because of asset shortage. The current necessitates that the world community improves future energy sources by developing sustainable, ecofriendly alternatives. In this work, biodiesel is produced through the transesterification of Catharanthus roseus seed oil with a barium-doped CaO heterogeneous nanocatalyst. The catalyst characterization is assessed using FTIR, GC-FID, EDAX, XRD, and SEM. The optimum conditions of time (70 min), temperature (58 °C), the molar ratio of methanol: oil is 15:1, and catalyst load (4% w/w) resulted in a conversion of the maximum biodiesel yield of 91.83%. Finally, by using Catharanthus roseus as a feedstock, the low optimal reaction conditions contribute to the development of the economic impact of biodiesel synthesis. Biodiesel blend (B20) containing barium-doped CaO nanoparticles showed better combustion engine performance and lower emissions than fossil fuels.