Objective To shorten the extraction time and increase the extraction yield of flavonoids from Nongxiangxing Baijiu Zaopei, and to identify the components and clarify the effectiveness of these flavonoids.Methods Nongxiangxing Baijiu Zaopei is used as the raw material and treated by the ultrasound-microwave-assisted aqueous two-phase extraction. With the total flavonoid extraction yield as the indicator, the extraction process is optimized by a response surface experiment. Then, the composition of the flavonoids from Zaopei is identified by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-QQQ-MS). Additionally, their effects on antioxidant reagents, α-amylase, and α-glucosidase are detected.Results The optimal extraction conditions for flavonoids from Zaopei are as follows: a liquid-to-material ratio of 49:1 (mL/g), an ethanol volume fraction of 66% in the aqueous two-phase system, 2.5 g of ammonium sulfate, ultrasonic treatment at 120 W for 25 min, followed by microwave treatment at 385 W for 42 s. Under these conditions, the flavonoid extraction yield reaches 14.75 mg/g. Thirty different flavonoid components are found in the flavonoids from Zaopei, with tangeretin being the most abundant (8 745.58 ng/g). Nine of these flavonoids are reported to possess both antioxidative and hypoglycemic/hypolipidemic effects. Activity assays show that the free radical scavenging activities of flavonoids from Zaopei against DPPH, ABTS⁺, and hydroxyl are 81.78%, 92.53%, and 81.37%, respectively. Their IC₅₀ values against α-amylase, α-glucosidase, and pancreatic lipase are 0.42 mg/mL, 0.32 mg/mL, and 3.70 mg/mL, respectively.Conclusion Compared with conventional ultrasound extraction, the ultrasound-microwave-assisted aqueous two-phase method significantly shortens the extraction time and increases the extraction yield of flavonoids from Zaopei. The extracted flavonoids demonstrate strong antioxidant, hypoglycemic, and hypolipidemic activities, indicating high application potential.