Antimicrobial resistance (AMR) hinders the effective treatment of a range of bacterial infections, posing a serious threat to public health globally, as it challenges the currently available antimicrobial drugs. Among the various modes of antimicrobial action, antimicrobial agents that act on membranes have the most promising efficacy. However, there are no consolidated reports on the shortcomings of these drugs, existing challenges, or the potential applications of phytochemicals that act on membranes. Therefore, in this review, we have addressed the challenges and focused on various phytochemicals as antimicrobial agents acting on the membranes of clinically important bacterial pathogens. Antibacterial phytochemicals comprise diverse group of agents found in a wide range of plants. These compounds have been found to disrupt cell membranes, inhibit enzymes, interfere with protein synthesis, generate reactive oxygen species, modulate quorum sensing, and inhibit bacterial adhesion, making them promising candidates for the development of novel antibacterial therapies. Recently, polyphenolic compounds have been reported to have proven efficacy against nosocomial multidrug‐resistant pathogens. However, more high‐quality studies, improved standards, and the adoption of rules and regulations are required to firmly confirm the clinical efficacy of phytochemicals derived from plants. Identifying potential challenges, thrust areas of research, and considering viable approaches is essential for the successful clinical translation of these compounds.