Alkaloids, a group of second metabolites from plants, possess great health benefits against various chronic diseases. Rhizome coptidis (Coptis chinensis Franch) is a commonly used traditional Chinese herb that contains abundant alkaloids but rarely used. In the present study, the effects of process variables on alkaloid content from rhizome coptidis were investigated, and extraction temperature above 80°C was found to have insignificant effect. To achieve maximal extraction of alkaloids from rhizome coptidis, a five-level, three-variable small composite design was employed, and optimal conditions of extraction time, ethanol concentration, and solvent to sample ratio were obtained using response surface methodology. Based on the analysis of variance results, extraction time, and solvent to sample ratio were identified as critical variables in extraction process, and the optimum extraction conditions were an extraction time of 133 min, ethanol concentration of 45%, and solvent to sample ratio of 42 v/w, and under these conditions, the experimental total alkaloid content was 15.96±0.15 g BCE/100 g, which well matched with the predicted value.