This study aimed to clarify the composition and application of the classic prescription Gancao Xiexin Decoction，so as to provide literature evidence support and scientific basis for its modern clinical application and drug development.Methods:Using the keyword “Gancao Xiexin Decoction”，The study searched ancient book databases and China National Knowledge Infrastructure(CNKI) and selected literature based on inclusion and exclusion criteria.In addition，its source，composition，usage and dosage，drug origin，processing methods，efficacy indications，and clinical application were summarized.Results:The original prescription of Gancao Xiexin Decoction was included in the Treatise on Febrile Diseases(Zhang Zhongjing in Han Dynasty)，and 107 effective entries were selected.Among them，89 ancient traditional Chinese medicine books were involved，and a total of 46 prescriptions were consistent with the original text.The prescription was mainly composed of six medicines：Glycyrrhizae Radix et Rhizom，Scutellaria Radix，dried ginger，Ziziphus jujuba，Rhizoma Pinelliae，and Coptis Rhizoma，of which Glycyrrhizae Radix et Rhizom，Scutellaria Radix，dried ginger，and Coptis Rhizoma had the highest frequency of 4:3:3:1，accounting for 77.52%，and all of them are raw except for Glycyrrhizae Radix et Rhizom，which was used as Glycyrrhizae Radix et Rhizoma Praeparata cum Melle.The clinical application of Gancao Xiexin Decoction was extensive，and it could treat multi-systemic diseases，of which the oral system disease accounts for the largest proportion of 34.19%.Its traditional Chinese medicine symptoms mainly included typhoid fever and distension，spleen-stomach weakness，fully demonstrating Zhang Zhongjing's diagnosis and treatment principle of “benefiting vitality and harmonizing the stomach，eliminating lumps and stopping vomiting”.Conclusion:Gancao Xiexin Decoction was first seen in the Han Dynasty，and the records of Gancao Xiexin Decoction in ancient books throughout history mostly follow the original prescription.Its modern clinical application scope gradually expands，but the disease is always related to “weakness of the spleen and the stomach”.