Licorice (Glycyrrhiza glabra) has a long history of use in traditional medicine, including traditional Chinese medicine and Ayurveda, for supporting the adrenal system and managing symptoms of "adrenal fatigue." Scientifically, licorice contains the compound glycyrrhizin, which inhibits the enzyme 11β-hydroxysteroid dehydrogenase type 2. This enzyme normally converts active cortisol to inactive cortisone. By inhibiting this conversion, glycyrrhizin can effectively prolong the action of endogenous cortisol, thereby mimicking or enhancing adrenal cortex function. Several studies have demonstrated that licorice can increase cortisol levels and may exert mild mineralocorticoid effects, which has led to its use as an adjunct in managing adrenal insufficiency.

However, clinical evidence remains limited in terms of large, high-quality human trials specifically evaluating licorice for adrenal support in otherwise healthy individuals. Most scientific validation comes from mechanistic studies and case reports, with some clinical use in managing Addison's disease and in settings where prolonged cortisol action is desirable. Potential adverse effects, such as hypertension, hypokalemia, and fluid retention, are well-documented and limit its prolonged or unsupervised use. In summary, licorice has a scientific basis for supporting adrenal cortex function, primarily through modulation of cortisol metabolism, but the strength of evidence is moderate and must be weighed against its safety profile.