Alcohol Use Disorder (AUD) is a highly prevalent medical condition characterized by impaired control over alcohol consumption, despite negative consequences on the individual's daily life and health. There is increasing evidence suggesting that chronic alcohol intake, like other addictive drugs, induces neuroinflammation and oxidative stress, disrupting glutamate homeostasis in the main brain areas related to drug addiction. This review explores the potential application of mesenchymal stem cells (MSCs)-based therapy for the treatment of AUD. MSCs secrete a broad array of anti-inflammatory and antioxidant molecules, thus, the administration of MSCs, or their secretome, could reduce neuroinflammation and oxidative stress in the brain. These effects correlate with an increase in the expression of the main glutamate transporter, GLT1, which, through the normalization of the extracellular glutamate levels, could mediate the inhibitory effect of MSCs’ secretome on chronic alcohol consumption, thus highlighting GLT1 as a central target to reduce chronic alcohol consumption.