Background: Compound medicines (traditional Chinese medicines [TCM] formulae) are the main means of treating diseases in TCM. Now, for the convenience of clinical use, there are a lot of Chinese patent medicines (proprietary Chinese medicine) on the market. However, the preparation of Chinese patent medicine needs to solve 2 key problems. One is as far as possible to keep crude drug's active ingredients, and the second is the cost control of industrialization; in this article, the extraction process for the proprietary Chinese medicine of the classic TCM formula, Duliang formula, has been studied effectively. Objective: To investigate the optimal ethanol-based extraction process for Duliang formula by central composite design and response surface methodology. Materials and methods: Central composite design was used to carry out a 3-factor 5-level study for a comprehensive evaluation of the extraction process of Duliang formula after normalization processing, with the ethanol concentration, solvent volume, duration, and times of extraction as investigation factors to consider; also, the contents of imperatorin, ferulic acid, and extract yield were determined as Quality Control indicators. Multiple linear regression, binomial fitting, and response surface methodology were used to analyze and determine the optimal ethanol-based extraction process for Duliang formula and predict its extraction parameters. Results: The determined optimal ethanol-based extraction process was thermal reflux extraction twice with 11 times of 90% ethanol for 2.5 h each time. The overall desirability for the “Normalization Value” evaluation was 0.7681, with a deviation of −0.99% (<5%) compared with the predicted value (0.7758). Conclusions: The determined ethanol-based extraction process for Duliang formula was easy and convenient, with stable, accurate, reliable parameters and reasonable predictability, and could serve as a reference for the industrial production of Duliang formula.