Antimicrobial resistance (AMR) has already been declared as the next pandemic. This has led to a paradigm shift towards the use of natural plant-based products called phytochemicals. The pace of discovery of new antibiotics is slower as compared to the increasing trend of AMR. To combat this threat, many efforts are directed to study phytochemicals as a suitable candidate in place of antibiotics. Research has increasingly highlighted their potential not only as stand-alone treatments but also as complementary agents to conventional antibiotics, enhancing their efficacy and overcoming resistance mechanisms. Additionally, the use of phytochemicals offers a more sustainable and less toxic alternative to synthetic antibiotics, thereby paving the way for safer therapeutic options. This chapter summarizes various approaches adopted for the better selection of phytochemicals to be used as antibacterial agents. These include both in-silico studies involving dynamic simulations and molecular docking as well as in-vitro trials to study the efficacy of various phytocompounds against bacterial pathogens. Nonetheless, significant physicochemical barriers such as low bioavailability, pharmacokinetic properties of the agent, low solubility of phytocompounds, limited gastrointestinal absorption, low hydrophilicity, and slow intrinsic dissolution impede the effective use of these natural compounds as treatments for various infections. However, the use of nanoparticle-driven phytocompounds is showing good results. As scientists continue to explore the rich diversity of plant secondary metabolites, the integration of antibacterial phytochemicals into clinical practice could herald a new era in infection management, promoting both health and environmental sustainability.