In the present research, an ultrasound-assisted extraction method was utilized to extract crocin from saffron samples using a variety of solvents, including water-miscible and water-immiscible organic solvents, ionic liquids, and deep eutectic solvents, prior to high-performance chromatography with a photodiode array detector. The extraction procedure was optimized using response surface methodology with the central composite design method, and the best conditions were determined with the aforementioned solvents. The results confirmed that better efficacy of deep eutectic solvents were more effective for extracting crocin compared to the other solvents tested, resulting in higher extraction recoveries. However, the volume required for crocin extraction using deep eutectic solvents was higher than that of organic solvents (approximately 300 µL versus 150 µL). The higher viscosities of deep eutectic solvents also led to a longer extraction time (13.6 min) compared to carbon tetrachloride (5.6 min) and methanol (5.8 min). The extraction recovery of crocin using choline chloride: ethylene glycol deep eutectic solvent reached 97.6% while other solvents yielded lower extraction the extraction recoveries. Finally, the developed method was successfully employed to the extract crocin from various saffron samples grown in different regions of Iran.