<p>This review critically examines the therapeutic potential of <i>Glycyrrhiza glabra</i> (licorice) and its bioactive compounds in supporting gastrointestinal health. The botanical profile, historical medicinal applications, and principal bioactive compounds, including glycyrrhizin, flavonoids, and polysaccharides, are described. Mechanistic insights reveal that <i>G. glabra</i> exerts multifaceted actions, including anti-inflammatory, antioxidant, immunomodulatory, barrier-enhancing, and microbiota-regulating effects, which contribute to the maintenance of intestinal homeostasis. An extensive evaluation of experimental and clinical studies demonstrates protective roles for <i>G. glabra</i> in disorders such as inflammatory bowel disease, gastritis, peptic ulcer disease, and irritable bowel syndrome. While clinical investigations and meta-analyses validate its symptom-alleviating properties and favorable safety profile at recommended dosages, potential adverse effects and contraindications warrant consideration. This review concludes by outlining current research gaps and highlighting future directions, emphasizing the need for rigorous clinical trials and mechanistic studies. Collectively, current evidence supports <i>G. glabra</i> as a promising phytopharmacological candidate for further investigation in the integrative management of gut inflammation, although additional clinical validation is required.</p> Graphical abstract <p></p>