The world’s human health is impacted by the unprecedented usage of antibiotics that resulted in the development of resistance. The emergence of resistance has raised the expense of treating illnesses and jeopardized the use of a wide variety of antibiotics. Because of the diseases’ diverse metabolic, genetic, and physiological aspects, the quick development of resistant microorganisms and the absence of a systematic management plan, researchers are now looking at plant-derived substances (PDSs) as an alternative to or in addition to antibiotics. Analytical techniques for their isolation, characterization, and phytochemical testing have been developed for use in the treatment of various diseases, considering the quantitative properties of plant constituents that attribute health benefits. PDSs such as polyphenols, alkaloids, and tannins have a lot of potential for application as antimicrobials or as modifiers of antibiotic resistance, and they could fight bacterial infections. The mechanisms by which PDSs aid in overcoming the increase in resistance, methods for screening various phytochemicals, techniques used to identify and test bioactive components, and tactics that could be used to combat the deadly effects of multidrug resistance are the main topics of this chapter.