Potential of Plant-Derived Phytochemicals in Combating Antimicrobial Resistance: A Comprehensive Review

Background: Antimicrobial resistance (AMR) represents a critical threat to global health, with drug-resistant infections projected to cause more deaths than cancer by 2050. Conventional antibiotics are increasingly failing due to misuse, overprescription, and the rapid evolution of resistance mechanisms. At the same time, innovation in antibiotic discovery has stagnated, creating an urgent need for alternative therapeutic strategies. Plant-derived phytochemicals have gained attention for their structural diversity, multi-target modes of action, and potential to reverse resistance mechanisms. Objective: This review aims to comprehensively evaluate the potential of plant-derived phytochemicals as novel antimicrobial agents and resistance-modifying adjuvants, highlighting their mechanisms of action, synergistic potential with conventional antibiotics, clinical applications, and translational challenges. Methods: A narrative review methodology was employed, sourcing relevant studies from PubMed, Scopus, Web of Science, and Google Scholar (2000–2025). Inclusion criteria focused on studies investigating the antimicrobial activity, molecular targets, synergistic interactions, and clinical relevance of plant-derived compounds. Results: Phytochemicals demonstrated activity across a wide microbial spectrum by inhibiting efflux pumps, disrupting membranes, interfering with DNA and protein synthesis, and enhancing antibiotic efficacy. Several compounds have progressed to clinical evaluation, showing efficacy in infections such as UTIs, respiratory diseases, and gastrointestinal infections. Conclusion: Plant-derived phytochemicals offer a promising adjunct or alternative to conventional antibiotics. Further mechanistic studies, optimized formulations, and rigorous clinical trials are essential for clinical translation.