The objective of this study was to extraction and evaluation of bioactive compounds from the aerial parts of Amygdalus lycioides. Three extraction methods were evaluated. Decoction using ethanol–water and methanol–water solvents at 70 °C for 30 min;

Maceration using ethanol–water and methanol–water solvents at 25 °C for 3 days; and

Ultrasonic-assisted extraction with ethanol–water and methanol–water solvents at 50 °C for 15 min under a continuous frequency of 40 kHz. The best extraction conditions were selected based on extraction yield, antioxidant activity, and total phenolic content (TPC) using a fuzzy inference system. The results indicated that the ultrasound-assisted extraction with ethanol–water solvent exhibited the highest antioxidant activity (86.26%) and total phenolic content (429.25 mg GAE/100 mL), while the decoction method with methanol–water showed the lowest values (76.80% and 325.08 mg GAE/100 mL, respectively). According to the fuzzy ranking, the ultrasound-assisted ethanol–water method obtained the highest score (89.2), followed by the ultrasound-assisted methanol–water method (88.5), whereas the other extraction methods had equal scores of 50. Furthermore, HPLC–MS analysis of the Amygdalus lycioides extract revealed the presence of abundant polyphenolic compounds such as Quercetin (26.66 µg/mg) and Caffeic acid (9.069 µg/mg). Considering the actual values of extraction yield, phenolic content, antioxidant activity, and solvent safety, the ultrasound-assisted ethanolic extraction was identified as the most suitable and best method.