Abstract: Depression is a common mental disorder, clinically manifested primarily by persistent low mood and loss of interest, imposing a heavy burden on patients and their families. Monoaminergic antidepressants are associated with issues such as delayed onset of action, low efficacy, and high relapse rates, thus failing to adequately meet clinical treatment needs of patients. Studies have demonstrated that the glutamatergic system plays a crucial role in the progression of depression. Drugs targeting glutamatergic receptors can achieve rapid, effective, and sustained antidepressant effects by modulating glutamate release and receptor signaling pathways. Currently, the only rapid-acting antidepressants targeting glutamatergic receptors that have been approved for marketing globally are Spravato and Auvelity, which fall far short of meeting the clinical needs in this field. This review summarizes the research progress in rapid-acting antidepressants targeting glutamatergic receptors, aiming to provide insights and references for the future development and clinical application of such drugs.