Glutamate is a major excitatory neurotransmitter in the central nervous system and a potential neurotoxin. During the development of depression, the glutamate concentration increases in the hippocampus. When glutamate accumulates, it causes serious damage to neurons and brain tissue, aggravating the depressive state. Therefore,glutamate accumulation may be a major mechanism of depression development. Astrocytes, glutamate transporters, and glutamate receptors play important regulatory roles in the glutamate concentration. This article reviews the mechanism-ofaction of traditional Chinese medicine on depression by regulating astrocytes, glutamate transporters, and glutamate receptors, and provides new ideas to explore treatment of depression by traditional Chinese medicine.