The emergence of antibiotic-resistant bacteria highlights the key magnitude of developing novel antimicrobials. Novel antimicrobials can be acquired from natural antimicrobials such as plants or herbs or their byproducts, animals, bacteria, algae, and mushrooms, which are officially recognized in India and consume (80%) 1.1 billion World Health Organization (WHO). New cultivation, genomic engineering techniques, and modern approaches are developed to generate novel narrow-spectrum antimicrobials. The review focuses on the safety and efficacy of several well-studied natural antimicrobials, some unique culture techniques, and current approaches to new antimicrobial development. It also discusses drivers, mechanisms of antimicrobial resistance (AMR), and strategies for reducing AMR. A conclusion is made on the fact that natural products are still an important source of novel antimicrobial agents and are particularly recommended by WHO due to their safety and efficacy and several positive health benefits. Furthermore, this review highlights important knowledge gaps and suggests future research to design chemically and structurally novel antimicrobials from natural products. Promoting cooperation between scientists, medical professionals, and decision-makers, we may use natural product capabilities fully to counter microbiological hazards and improve worldwide health results. The application of nanotechnology greatly enhanced the effectiveness of naturally derived antimicrobials against several microbial diseases.
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