The superior bioavailability and bioactivity of glycyrrhetinic acid (GT) as a food supplement, has always been a research focus in the food industry. This study aims to extract glycyrrhizic acid (GA) from Glycyrrhiza glabra using ultrasound radiation and then simultaneously hydrolyze to and separate GT using a novel approach involving a nanoemulsion medium. The extraction of GA was optimized using response surface methodology (RSM) to determine the optimal time, liquid-to-solid ratio, and ammonia percentage, resulting in a 9% extraction yield. Additionally, the parameters for the simultaneous hydrolysis and separation steps were optimized, achieving 92.6% and 63.7% efficiency, respectively. The use of immiscible and nanoemulsified organic solvent, produced through ultrasound radiation, significantly improved the efficiency, as confirmed by particle size analysis and microscopic magnification. The extraction yield of GA and the resulting product of GA hydrolysis were analyzed using HPLC, and the product's chemical structure was confirmed by mass spectrometry. The results demonstrated that the sonication technique reduced extraction time by nearly half compared to conventional solvent extraction, and selecting the appropriate organic solvent through making a nanoemulsion medium, greatly improved GT purity. Ultrasound-assisted extraction of glycyrrhizic acid, simultaneous hydrolysis of glycyrrhizic acid, and separation of glycyrrhetinic acid are reported.Using response surface methodology (RSM), the extraction yield of glycyrrhizic acid increased to 9%.Optimization of the hydrolysis conditions resulted in a 92.6% conversion productivity of glycyrrhizic acid to glycyrrhetinic acid.Adding immiscible organic solvents during ultrasonication, significantly improved the glycyrrhetinic acid extraction efficiency by nanoemulsification/extraction.HPLC/mass spectrometry analysis was conducted to confirm the chemical structure of the final product.