Rubus alceifolius Poir (R.A. Poir) leaves are rich in phenolic compounds, offering many health benefits due to their incredible antioxidant potential. In this study, conditions for the ultrasound-assisted extraction (UAE) of phenolic compounds and antioxidant activity from R.A. Poir leaves were optimized using response surface methodology (RSM). This methodology assessed the effects of ultrasound power (X1: 100-500 W), extraction temperature (X2: 30-60°C), and extraction time (X3: 5-55 min). The optimized UAE conditions were then compared with conventional extraction methods (Soxhlet extraction: SE and maceration extraction: ME) for extracting total phenolics. A phenolic profile using GC-MS and antioxidant activity (ABTS) was also compared. According to the RSM, the best conditions for UAE to extract the highest total polyphenol content and ABTS radical scavenging activity were 320 W ultrasound power, 40°C extraction temperature, and 35.5 min sonication duration. Under these optimal conditions, the TPC and antioxidant activity reached 16.68 mg GAE/g dm and 21.9 mg TE/g, respectively, closely aligning with the predicted values. The UAE extraction technique proved to be more efficient in extracting phenolics and antioxidant capacity (ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)) radical scavenging activity, and enzyme inhibition) compared to the conventional extraction methods (SE and ME). A GC-MS analysis identified 12 components, including 5 phenolics and 3 flavonoids, which likely contribute to the antioxidant activity. Consequently, the UAE method improved extraction efficiency within a shorter time frame, suggesting that UAE is a promising, efficient, and ecofriendly technology for extracting bioactive compounds from R.A. Poir leaves.