The article reviews the role of glial cells in mood disorders and substance use disorder (SUD), highlighting their contributions to neuroinflammation, neurotrophic factors, and gut microbiota. Glial cells, including microglia, astrocytes, oligodendrocytes, and synantocytes, play crucial roles in maintaining neuronal function and homeostasis. Microglia, the primary immune cells in the brain, are involved in neuroinflammation and synaptic plasticity, which are key factors in mood disorders and SUD. Astrocytes, which provide structural support and regulate neurotransmitter levels, also contribute to these disorders through their interactions with neurons. Oligodendrocytes, responsible for myelination, can influence mood and addiction through their role in white matter integrity. Synantocytes, or NG2 cells, are involved in neuronal plasticity and neuroinflammation, potentially affecting mood and addiction. The article discusses the potential therapeutic targets for novel interventions in mood disorders and SUD, emphasizing the importance of understanding glial-neuron interactions.The article reviews the role of glial cells in mood disorders and substance use disorder (SUD), highlighting their contributions to neuroinflammation, neurotrophic factors, and gut microbiota. Glial cells, including microglia, astrocytes, oligodendrocytes, and synantocytes, play crucial roles in maintaining neuronal function and homeostasis. Microglia, the primary immune cells in the brain, are involved in neuroinflammation and synaptic plasticity, which are key factors in mood disorders and SUD. Astrocytes, which provide structural support and regulate neurotransmitter levels, also contribute to these disorders through their interactions with neurons. Oligodendrocytes, responsible for myelination, can influence mood and addiction through their role in white matter integrity. Synantocytes, or NG2 cells, are involved in neuronal plasticity and neuroinflammation, potentially affecting mood and addiction. The article discusses the potential therapeutic targets for novel interventions in mood disorders and SUD, emphasizing the importance of understanding glial-neuron interactions.