Abstract: The study aims to establish and validate a mouse model of depression with concurrent heart and spleen deficiency using a combined induction method involving neurobehavioral assessments and traditional Chinese medicine (TCM) syndrome evaluation. The model was constructed via modified electroshock and forced swimming protocols, and compared to a chronic unpredictable mild stress (CUMS)-induced depression model. Syndrome validation was performed using TCM prescriptions. Depression assessments revealed that the mice in the combined induction model exhibited significant depressive-like behaviors compared to controls. Moreover, the 5-hydroxytryptamine (5-HT) and dopamine (DA) levels in the brain tissue and serum were significantly decreased (P < 0.01, P < 0.05), while corticosterone (Cor) levels were significantly increased (P < 0.01). TCM syndrome evaluation demonstrated symptoms including mental fatigue, delayed responses, insomnia, reduced appetite (P < 0.01), and diminished tongue color intensity (P < 0.01). Cardiovascular and digestive functions were impaired (P < 0.01, P < 0.05), with a decreased spleen index (P < 0.01). Validation experiments indicated that paroxetine alleviated the depressive-like behaviors, while the classic TCM formula Guipi Decoction significantly modulated depression-related biomarkers and syndrome indicators. A mouse model of depression with both heart and spleen deficiency can be successfully established using the modified electroshock combined with forced swimming method. Animal experiments were conducted with the approval and supervision of the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (ethics number: 2023031303).