Abstract: To achieve green and efficient polyphenol extraction from millet, this study used an ion-responsive deep eutectic solvent (DES) with ultrasound-assisted extraction, elucidating a novel approach for rapid separation of millet polyphenols. This study determined the effects of molar ratio of DES components, DES water content, solid-to-liquid ratio, ultrasound time, and ultrasound temperature on millet polyphenol yield. Our extraction process was optimized using response surface methodology, and we analyzed millet polyphenol extract antioxidant capacity. This study also assessed extraction method greenness, and compared our process with traditional ethanol extraction. After extraction, the solvent could be simply recovered and reused by adding sodium chloride to the extract. The optimal conditions were butyric acid-urea DES with a 4:1 molar ratio, 38% water content, a solid-to-liquid ratio of 1:10 g/mL, 15 min ultrasound time, and 57 ℃ ultrasound temperature. Under these conditions, 3.76±0.13 mg/g millet polyphenols were obtained. In vitro antioxidant tests demonstrated considerable antioxidant activity, with positive correlation with its concentration. The DES extract exhibited respective DPPH and hydroxyl radical scavenging rates of 95.14% and 89.13%, both higher than those recovered by ethanol extraction. In Analytical Eco-Scale (AES) assessment, the DES method scored 92 points, compared with 85 points for the ethanol method. In evaluations using the Analytical GREEnness (AGREE), Analytical GREEnness Metric for Sample Preparation (AGREEprep), and Green Analytical Procedure Index (GAPI) scales, our DES extraction method exhibited larger green areas in the respective pictograms, demonstrating its superior greenness compared with conventional ethanol extraction. The ion-responsive DES developed in this study shows promise for green extraction and separation of bioactive compounds.