Background: The herbs should be processed by different methods before use, and the efficacy and toxicity of Chinese herbal medicines may change, which may enhance efficacy and reduce toxicity after processing. Gansui (Kansui radix) is a common clinical herbal medicine, and there are considerable changes in its toxicity and efficacy after processing. Gaocao (Glycyrrhizae radix et rhizome) has a detoxifying effect. Methods: Using the contents of euphorbiadienol and the alcohol-soluble extract of Glycyrrhizae radix-processed Kansui radix as evaluation indexes, response surface methodology was used to optimize the processing technology of Kansui radix by exploring the effects of Glycyrrhizae radix et rhizoma-addition amount, frying temperature, and frying time on the processing technology of Kansui radix. Meanwhile, response surface software was used to analyze experimental data to determine the processing parameters of Kansui radix by Glycyrrhizae radix et rhizoma. Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine is used to analysis the potential ingredients of Kansui radix and verify the potential ingredients by western blotting. Results: The technology of Glycyrrhizae radix et rhizoma-processed Kansui radix was optimized for the Glycyrrhizae radix et rhizoma-addition amount of 27％, frying temperature of 180 °C, and frying time of 11 min. The network pharmacology analysis revealed that Kansui radix could cause kidney, liver, and heart injury by the PI3K/AKT signaling pathway. Kansui radix at high or low dose could decrease the ratio of p-AKT/AKT while Glycyrrhizae radix et rhizoma-processed Kansui could increase it. Conclusion: The model established by response surface methodology is relatively accurate and can predict the contents of euphorbiadienol and alcohol extract of processed Kansui radix. The toxic effects and its mechanism of action of Kansui radix and processed Kansui radix on kidney, liver, and heart, from the perspective of systems biology, have provided scientific evidence to its clinical application.