Liver depression syndrome (LDS) is commonly observed in various clinical diseases. Extensive studies have demonstrated that chronic stress serves as the primary trigger for LDS, and its biological mechanisms closely related to the changes in the morphology and function of multiple central brain regions. However, the relevant evidence remains scattered across numerous studies, necessitating further synthesis and review. Based on this, this paper reviews the animal modeling and evaluation methods of LDS, the relationship between LDS pathogenesis and morphological, functional, and molecular changes in brain regions such as the hippocampus, cortex, hypothalamus, locus coeruleus, striatum, and amygdala, as well as the regulatory effects of traditional Chinese medicine (TCM). The findings provide a foundation and direction for further research into the biological basis of LDS, the identification of syndrome-specific targets, and the exploration of therapeutic mechanisms of TCM compounds.