The article provides a comprehensive overview of metabotropic glutamate receptors (mGluRs), which are family C G-protein-coupled receptors (GPCRs) involved in modulating synaptic transmission and neuronal excitability in the central nervous system (CNS). mGluRs bind glutamate within their large extracellular N-terminal domain and transmit signals through intracellular signaling pathways. The article discusses the structural features of mGluRs, including the Venus Flytrap Domain (VFD), cysteine-rich domains (CRDs), and the heptahelical domain (HD). It also covers the signaling mechanisms, such as activation, general signaling profiles, and the role of alternative splicing and protein-protein interactions. The pharmacological profiles of mGluRs, including orthosteric and allosteric ligands, are detailed, highlighting the development of highly selective ligands for different subtypes. The functional roles of mGluRs in various CNS functions, such as synaptic plasticity, neuronal excitability, and neurotransmitter release, are discussed. The therapeutic potential of mGluRs in treating neurological and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, anxiety, depression, and schizophrenia, is explored. The article concludes by emphasizing the rapid advancements in the field of mGluRs and their potential for future therapeutic applications.The article provides a comprehensive overview of metabotropic glutamate receptors (mGluRs), which are family C G-protein-coupled receptors (GPCRs) involved in modulating synaptic transmission and neuronal excitability in the central nervous system (CNS). mGluRs bind glutamate within their large extracellular N-terminal domain and transmit signals through intracellular signaling pathways. The article discusses the structural features of mGluRs, including the Venus Flytrap Domain (VFD), cysteine-rich domains (CRDs), and the heptahelical domain (HD). It also covers the signaling mechanisms, such as activation, general signaling profiles, and the role of alternative splicing and protein-protein interactions. The pharmacological profiles of mGluRs, including orthosteric and allosteric ligands, are detailed, highlighting the development of highly selective ligands for different subtypes. The functional roles of mGluRs in various CNS functions, such as synaptic plasticity, neuronal excitability, and neurotransmitter release, are discussed. The therapeutic potential of mGluRs in treating neurological and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, anxiety, depression, and schizophrenia, is explored. The article concludes by emphasizing the rapid advancements in the field of mGluRs and their potential for future therapeutic applications.