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 chlorogenic acids and anthocyanins in 15 blueberry samples. Correlation analysis showed that the contents of chlorogenic acid, neochlorogenic acid, and cryptochlorogenic acid were significantly negatively correlated with DPPH and ABTS⁺ radical scavenging rates, and significantly positively correlated with FRAP and RP. The contents of delphinidin-3-galactoside and delphinidin-3-arabinoside were significantly positively correlated with FRAP and RP, and negatively correlated with ABTS⁺ radical scavenging rate, but only the correlation for delphinidin-3-arabinoside was significant. In contrast, delphinidin-3-glucoside was significantly positively correlated with ABTS⁺ radical scavenging rate, and significantly negatively correlated with FRAP and RP. Among cyanidin, petunidin, peonidin, and malvidin, only cyanidin-3-glucoside was significantly negatively correlated with FRAP and RP, while petunidin-3-galactoside and petunidin-3-arabinoside were significantly positively correlated with FRAP and RP. 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. In summary, 20~60 μg/mL CGAE and 15~25 μg/mL ANTE significantly reduced ROS levels while significantly increasing the activities of GSH-Px and SOD, and the antioxidant effect of ANTE was significantly higher than that of CGAE. This study screened blueberry extracts with high antioxidant activity, providing a reference for research on the antioxidant applications of blueberry extracts.