Depression is known as “Yu Zheng” in traditional Chinese medicine (TCM). Jiuwei Zhenxin granules (JZG) is a type of TCM. According to TCM theory, it nourishes the heart and spleen, tonifies Qi, and tranquilizes the spirit, and may also has effects in the treatment of depression. Here, we systematically reviewed recent basic and clinical experimental studies of JZG and depression, including studies of the pharmacological mechanisms, active ingredients, and clinical applications of JZG in depression treatment. This review will deepen our understanding of the pharmacological mechanisms, drug interactions, and clinical applications of TCM prescriptions and provide a basis for the development of new drugs in the treatment of depression.