ABSTRACT Rose myrtle fruits contain high levels of phenolics and other bioactive compounds. To enhance the extraction efficiency of these phenolic compounds, ultrasound-assisted deep eutectic solvent (UA-DESs) extraction has been proposed. Initially, six distinct DESs were utilized in this study and compared with traditional solvents (ethanol, methanol, and hexane). The most suitable solvent for extracting phenolic compounds from rose myrtle fruits was determined to be choline chloride: urea (with a molar ratio of 1:2). Following that, the Box-Behnken design was employed to identify the optimal extraction conditions (ultrasonic power (X1), solid to liquid ratio (X2), and extraction time(X3))forachievinghightotalphenoliccontent(TPC)andantioxidantactivity(IC50). Resultsdemonstratedthatthe optimum ultrasound-assisted DES extraction parameters for attaining the highest TPC and antioxidant activity (IC50) (85.19 mgGAE/g fresh fruit and 2.31 mg/g, respectively) were X1 of 233 W, X2 of 440 mg/mL, and X3 of 55 minutes. In comparison to traditional maceration extraction, extracts obtained through UA-DES extraction exhibited higher TPC and antioxidant activity (IC50), while requiring less extraction time. Scanning electron microscopy images (SEM) disclosed that the dissolution of bioactive components was enhanced due to cell disruption after ultrasound-assisted DES extraction. Consequently, the amalgamation of UA-DESs offers an exceptional extraction technique for the efficient retrieval of bioactive components from rose myrtle fruit. KEYWORDS Rose myrtle fruits; Deep eutectic solvents (DESs); Ultrasound-assisted DESs extraction; Phenolic compounds