Polyphenolic compounds in Glycyrrhiza spp.: a potential weapon against multidrug-resistant pathogens

Antimicrobial resistance (AMR) is a rapidly escalating global health crisis, projected to cause 10 million deaths annually by 2050 without effective intervention. Conventional antibiotics are increasingly compromised by multidrug-resistant (MDR) pathogens that deploy mechanisms such as efflux pumps, membrane impermeability, target modification, and biofilm formation. Polyphenolic compounds from Glycyrrhiza spp (<i>licorice</i>) represent a promising, multi-target strategy to counter these threats. This review critically examines the antimicrobial potential of licorice-derived flavonoids, chalcones, coumarins, and glycosides, focusing on their ability to inhibit efflux pumps, disrupt bacterial membranes, prevent biofilm formation, modulate quorum sensing, and synergize with conventional antibiotics. We integrate mechanistic insights with safety, pharmacokinetic, and formulation considerations, highlighting both therapeutic potential and translational challenges. Evidence indicates that licorice polyphenols can restore antibiotic efficacy against MDR bacteria, reduce the likelihood of resistance development, and be incorporated into topical agents or antimicrobial materials. However, limitations in bioavailability, dose-dependent toxicity, and a paucity of clinical trials underscore the need for targeted delivery systems and rigorous <i>in vivo</i> validation. By framing licorice polyphenols as risk-mitigating agents, this review positions them as viable candidates for next-generation adjunctive therapies and preventive strategies in the fight against AMR. In particular, their role against high-priority ESKAPEE pathogens and their inherent antioxidant properties further enhance their therapeutic value. This review therefore not only synthesizes current knowledge but also outlines future directions for translating licorice-derived polyphenols into clinical and industrial applications.