Abstract: To elucidate the composition of chlorogenic acid homologs and anthocyanins in blueberry extracts and their protective effects on human L-02 hepatocytes, the present study utilized organic solvent extraction and macroporous adsorption resin separation to prepare chlorogenic acid extracts (CGAE) and anthocyanin extracts (ANTE) from 15 blueberry samples of distinct cultivars, origins, and geographical locations. In vitro experiments were conducted to assess free radical scavenging capacity and evaluate the activity of antioxidant enzymes in L-02 hepatocytes. The results showed that chlorogenic acid > neochlorogenic acid > cryptochlorogenic acid > isochlorogenic acid B > isochlorogenic acid A > isochlorogenic acid C and delphinidin > petunidin > peonidin > malvidin > cyanidin in the average content of the 15 blueberry samples. Chlorogenic acid, neochlorogenic acid, and cryptochlorogenic acid were significantly correlated with ABTS, FRAP, DPPH, RP and delphinidin was significantly correlated with ABTS, FRAP, RP by correlation analysis. The results indicated that the active component content and antioxidant activity of blueberries varied significantly depending on the different cultivars, growing regions, and geographical origins. Principal component analysis (PCA) was employed to statistically validate the distinct chemotypic profiles among different varieties. A functional validation model at the cellular level was established, and the optimal induction conditions were determined as treatment with 350 μmol/L t-BHP for 4 hours. Using this optimized model, the protective effects of both CGAE and ANTE extracts were rigorously evaluated. The results demonstrated that: ROS level was significantly reduced, the activity of GSH-Px and SOD was significantly increased after administration of 20 μg/mL−60 μg/mL CGAE and 15 μg/mL−25 μg/mL ANTE by 350 μmol/L tert-butyl hydroperoxide (t-BHP) induced oxidative damage model in L-02 cells, and the antioxidant effect of ANTE was significantly higher than that of CGAE. Aiming to screen blueberry extracts with high antioxidant activity, providing a reference for research on the antioxidant applications of blueberry extracts.