Plant-derived compounds have attracted considerable attention in the field of antimicrobial therapy. This interest is primarily due to their natural origin and historical evidence of their use in traditional medicine systems. These derivatives are a rich reservoir of chemical diversity that has a promising potential for the development and production of new antimicrobial agents with the least amount of side effects and risks of drug resistance. However, the delivery of plant-derived antimicrobial agents, especially through the topical route, poses significant challenges. As the largest organ of the body, the skin acts as a first barrier against the entrance of microbial pathogens. A primary limitation to transdermal delivery of plant-derived antimicrobial agents is their complex molecular structures, which often prevent effective absorption through the skin. Therefore, developing and promoting an effective local drug delivery system to increase the potential of antimicrobial therapy is very important and effective in public health. This review discusses delivery strategies for plant-derived antimicrobial agents aimed at the bioavailability and stability of these compounds as well as their mode of action, ensuring targeted delivery to the site of infection with long-lasting effects and minimizing side effects. Besides, various topical drug delivery platforms are analyzed, including nanoparticles, liposomes, and innovative application methods such as microneedles.