Objective: This study aimed to optimize the preparation process of blueberry juice and improve its antioxidant activity. Methods: Blueberry juice was prepared using a wet ultrafine grinding process and compound enzymolysis method. Response surface methodology was used to optimize the process parameters and analyze the antioxidant activity of blueberry juice. Results: There were significant differences in the juice yield and active substance content of blueberry juice under different solid-liquid ratios, crushing times, compound enzyme contents, and enzymatic hydrolysis times, with enzymatic hydrolysis time having the most significant impact on juice yield and anthocyanin content. The optimal process parameters for the wet ultrafine grinding process and compound enzymolysis method are solid-liquid ratio of 1∶1.7 (g/g), pulverization time of 8.00 min, compound enzyme content of 0.15%, and enzymatic hydrolysis time of 127 min. Under the control of these process conditions, the blueberry juice yield was 87.89%, with the contents of anthocyanin, total flavonoid and total phenol were 612.04 mg/L, 2.96 g/L and 3.43 g/L, respectively, and its antioxidant capacity was equivalent to 0.3% vitamin C when the addition amount is 1.6 mL. Conclusion: The wet ultrafine grinding process and compound enzymolysis method can improve the juice yield of blueberry juice, maximize the retention of its active substances, and enhance its antioxidant capacity.