Cell envelope proteases (CEPs) can break down milk protein into peptides with different functions, which are of great benefit to human health. Therefore, the high-yield CEPs of Lactobacillus plantarum have the potential to produce functional dairy products. In previous experiments, we found that Na2HPO4, inulin, casein peptone and leucine have significant effects on CEP production by Lactobacillus plantarum LP69. So we proceeded to optimize the composition of the CEP-producing culture medium of L. plantarum through Box-Behnken design and response surface methodology. The protease activity, protein content and specific activity of CEPs produced by L. plantarum by inulin (0.2, 0.3, 0.4 %), casein peptone (0.4, 0.6, 0.8 %), Na2HPO4 (0.50, 0.52, 0.54 %) and leucine (14, 16, 18 mg/L) were evaluated. The optimal ratio of medium is 0.4 % inulin, 0.66 % casein peptone, 0.5 % Na2HPO4 and 14.04 mg/L Leucine. The final enzyme activity reached (24.46±0.81) U/mL, and the specific activity reached (1.41±0.46) U/mg.