Plant-derived antimicrobial compounds are essential in combating infections in traditional and modern medicine. Various biologically active components, including natural plant extracts, essential oils, phenolic compounds, flavonoids, alkaloids, and terpenoids, exhibit diverse antimicrobial effects against viral pathogens, bacteria, and fungi. Antibiotic resistance has become a global health concern, prompting accelerated research into plant-derived antimicrobials as potential alternatives to conventional treatments. This section will discuss the mechanisms of action, bioavailability, synergistic effects, and pharmacological potentials of plant-derived antimicrobial compounds. Additionally, the integration of traditional plant medicines with modern biotechnological strategies will be discussed, with a focus on innovative methods for incorporating these compounds into the pharmaceutical industry. In light of data obtained from clinical trials and in vitro/in vivo studies, the efficacy and safety profiles of these compounds will be evaluated, and potential solutions for overcoming antimicrobial resistance will be presented. As a result, a comprehensive perspective will be provided on how plant-derived antimicrobials can be utilized more effectively in sustainable healthcare systems.