[Objective] This study aimed to optimize the process of deep eutectic solvent extraction of flavonoids from exocarpium Citri grandis and to evaluate its antioxidant activity. [Methods] The type of deep eutectic solvent system, the water content of deep eutectic solvent, material-to-liquid ratio, extraction temperature, and extraction time were selected as experimental variables, and the yield of flavonoids was used as response variables to conduct single factor experiment. Then the single factors with significant differences were screened to optimize the process of deep eutectic solvent extraction of exocarpium C. grandis flavonoids by response surface methods. Finally, the scavenging ability of exocarpium C. grandis flavonoid extract on DPPH radicals, ABTS radicals, and hydroxyl radicals was explored to analyze the antioxidant activity. [Results] The highest yield of exocarpium C. grandis flavonoid was obtained by the choline chloride-glycol system. The yield of flavonoids was significantly impacted by the deep eutectic solvent's water content, the material-to-liquid ratio, and the extraction temperature. The response surface method was used to determine the ideal flavonoid extraction procedure, which included the deep eutectic solvent's water content of 43%, the material-to-liquid ratio of 1∶21 (g/mL), and the extraction temperature of 60 ℃. The yield of exocarpium C. grandis flavonoids was (19.31±0.47) mg/g. The results of antioxidant activity showed that the concentration for 50% of maximal effect values of DPPH radical, ABTS radical, and hydroxyl radical scavenging were (117.61±1.71), (36.91±0.46), (387.52±1.85) μg/mL. [Conclusion] The extraction of exocarpium C. grandis flavonoids using deep eutectic solvent resulted in significantly higher yields compared with conventional water and ethanol method. These flavonoid extracts had potential as a source of natural antioxidants.