The purpose of this study was to optimize the total anthocyanin content (TAC), total phenolic content (TPC), and antioxidant activity of acidified water extract from blue honeysuckle berries by response surface methodology (RSM). The optimized conditions were HCl concentration of 0.35%, liquid–solid ratio of 49.42 ml/g, and extraction temperature of 41.56°C for total anthocyanin content (24.01 ± 0.37 mg/g), total phenolic content (207.03 ± 3.31 mg/g), DPPH radical scavenging activity (68.24 ± 1.13%), and ABTS radical scavenging activity (70.05 ± 0.84%). The experimental results are consistent with the predicted values. The results showed that acidified water extraction was an effective, simple, and green technique for the extraction of total anthocyanins, total phenol, and antioxidant activity from blue honeysuckle berries.