A fatty acid alkyl ester can be made from Citrullus Colocynthis oil instead of pure diesel, since it has a higher ratio of triglycerides to monoglycerides. In the current study, the aim of the experimental work was to investigate combustion, emissions, and performance using biodiesel blends derived from Citrullus Colocynthis. A comparison of the qualities of pure Citrullus Colocynthis oil (100% biodiesel), pure diesel (100% diesel), and blended Citrullus Colocynthis and biodiesel (B20, B25, B50, and B75) is presented in the study. The B20 biodiesel blends are the most efficient because of their lower emission concentrations and higher thermal efficiency. Citrullus Colocynthis oil and its blends result in lower in-cylinder pressure and heat release rates. Compared to diesel fuel, a B20 blend performs better and produces less pollution. The test results showed an 18% reduction in HC emissions, a 35% reduction in CO emissions, a 33% reduction in smoke emissions, a 20% reduction in NOx emissions, and a 10% reduction in brake thermal efficiency.