Antibacterial Plant Secondary Metabolites: Mechanisms of Action, Pharmacokinetics, Safety, and Translational Potential

Antimicrobial resistance (AMR) has intensified the need for antibacterial agents with alternative chemical scaffolds and mechanisms of action. Plant-derived antibacterial compounds represent a chemically diverse source of bioactive molecules, but their therapeutic potential depends not only on in vitro potency but also on mechanistic validation, pharmacokinetic exposure, pharmacodynamic relationships, and biological safety. This review critically examines evidence published from 2014 to 2026 on major classes of plant-derived antibacterial compounds, emphasizing bacterial susceptibility, mechanisms of action, pharmacokinetics, and safety. Reported antibacterial effects include alterations in the cell envelope and membrane, disruption of energy metabolism, inhibition of protein synthesis and nucleic acid-associated targets, efflux and resistance modulation, and interference with quorum sensing, biofilm formation, and virulence. However, mechanistic evidence varies substantially among studies. Pharmacokinetic data reveal marked heterogeneity in absorption, bioavailability, tissue distribution, metabolism, protein binding, and elimination, while quantitative integration of antibacterial potency with active exposure and PK/PD remains limited. Cytotoxicity and in vivo toxicity studies further indicate that selectivity and tolerability are compound-, formulation-, dose-, and model-dependent. Overall, therapeutic translation requires integration of chemically defined antibacterial activity, validated mechanisms, infection-site exposure, PK/PD, host–cell selectivity, systemic safety, and efficacy in relevant infection models.