Abstract Only three medications are approved by the Food and Drug Administration (FDA) to treat Alcohol Use Disorder (AUD), and novel pharmacological targets are desperately needed. AUD is characterized by dysregulated motivation for and consumption of alcohol, and targets that affect motivated and consummatory behavior may hold promise. One such target is glucagon-like peptide-1 (GLP-1), a peptide hormone that regulates blood sugar and food intake. GLP-1 receptors are widely expressed in reward-related brain areas, and in preclinical models, GLP-1 agonists, which are FDA-approved for the treatment of Type 2 diabetes and obesity, appear to reduce the rewarding properties of both food and alcohol. Preclinical, human laboratory, and pharmacoepidemiologic data suggest that GLP-1 agonists would be beneficial for AUD, but to date only one trial, of the injectable GLP-1 agonist exenatide, has been conducted; it suggested exenatide was most effective for reducing drinking among patients with higher body mass. A particularly promising GLP-1 agonist for AUD treatment is semaglutide, which is pharmacologically optimized to increase plasma viability and, unlike other GLP-1 agonists that are formulated as subcutaneous injectables, is available in an oral formulation. We propose to conduct an exploratory randomized controlled trial (RCT) of oral semaglutide among treatment- seeking individuals with AUD. We will randomly assign 40 participants to receive semaglutide (titrated to 7 mg per day) or matched placebo for 8 weeks. Our primary aims are to assess the safety and tolerability of semaglutide in this population and to evaluate its effects, relative to placebo, on alcohol cue-elicited craving and alcohol consumption. Data from the proposed trial will support a subsequent proposal to conduct a larger RCT of oral semaglutide. Results from this proposal will be used to inform design choices for this larger trial. If successful, this line of work could ultimately lead to a novel pharmacological treatment option for AUD.