This article investigates a novel method for increasing the yield of methyl ester through alkali-catalyzed transesterification of Xanthium Spinosum in a cavitation reactor. The effects of the oil to methanol molar ratio (1:4 – 1:7), catalyst loading concentration (0.50-1.2 wt. percent), and reaction temperature (50.0 – 65.0 °C) were investigated using an adapted orifice plate with 21 (1 mm diameter) holes and a 2 bar inlet pressure in a 50 L Hydrodynamic Cavitation (HC) reactor assisted by a double diaphragm pump. A maximum conversion of 98.8 wt. percent was achieved in 25 minutes in an HC reactor with a 1:6 molar ratio of oil to methanol, 1.0 wt.% catalyst and a reaction temperature of 60 °C. The optimal reaction time for transesterification was reduced significantly (approximately fivefold) from 90 minutes for the mechanical stirring approach to 25 minutes for the HC approach. The sustainable raw material is capable to produce cleaner production of esters by adopting HC technology.