The accelerating emergence of antimicrobial resistance (AMR) has severely undermined the efficacy of conventional antibiotics, creating an urgent need for novel therapeutic strategies with broader and more sustainable antimicrobial potential. Medicinal plants offer a chemically diverse reservoir of bioactive metabolites, including alkaloids, flavonoids, terpenoids, tannins, and phenolic acids, that exhibit potent activity against a wide range of emerging and multidrug-resistant (MDR) pathogens. These phytochemicals act through multiple complementary mechanisms such as membrane disruption, efflux pump inhibition, quorum-sensing interference, enzyme suppression, and biofilm degradation, thereby countering bacterial survival strategies that contribute to AMR. Contemporary spectroscopic and chromatographic analyses, supported by metabolomics and network pharmacology, have enhanced the identification and mechanistic understanding of these compounds. Furthermore, several medicinal plants demonstrate additional gastroprotective, anti-inflammatory, and urease-inhibitory activities, making them promising candidates for the management of Helicobacter pylori–associated peptic ulcer disease. Synergistic interactions between plant extracts and conventional antibiotics further improve therapeutic efficacy by lowering minimum inhibitory concentrations and restoring antibiotic sensitivity in resistant strains. Despite substantial preclinical evidence, challenges such as poor phytochemical standardization, variability in plant composition, and limited clinical validation continue to hinder translation into mainstream therapy. Bridging these gaps requires rigorous quality control, advanced analytical profiling, and well-designed clinical studies. Overall, plant-derived antimicrobials hold significant potential as complementary or alternative strategies to address the global AMR crisis and strengthen future infectious disease management.
