Traditional Chinese medicine (TCM) is an ancient medical system with a unique cultural background. Nowadays, more and more Western countries due to its therapeutic efficacy are accepting it. However, safety and clear pharmacological action mechanisms of TCM are still uncertain. Due to the potential application of TCM in healthcare, it is necessary to construct a scientific evaluation system with TCM characteristics and benchmark the difference from the standard of Western medicine. Model organisms have played an important role in the understanding of basic biological processes. It is easier to be studied in certain research aspects and to obtain the information of other species. Despite the controversy over suitable syndrome animal model under TCM theoretical guide, it is unquestionable that many model organisms should be used in the studies of TCM modernization, which will bring modern scientific standards into mysterious ancient Chinese medicine. In this review, we aim to summarize the utilization of model organisms in the construction of TCM syndrome model and highlight the relevance of modern medicine with TCM syndrome animal model. It will serve as the foundation for further research of model organisms and for its application in TCM syndrome model.