Throughout history, natural products have played a major role in the discovery of drugs, especially cancer and infectious diseases. Natural products and their similarity and historical composition have contributed greatly to the healing of medicine. However, natural products have their own drug discovery challenges, such as technical barriers to testing, classification, performance, and efficiency, leading to a reduction in their research by the pharmaceutical industry. In recent years, many technological and scientific advances, including improved analytical tools, genetic engineering, engineering techniques, and the development of microbial farming, are facing these challenges and opening up new opportunities. Here, we summarize the latest technological advances that enable the availability of drugs for natural products, highlight selected applications and discuss key opportunities. Recent advances in genomics and structural biology over the past few decades paint a vivid picture of protein variations targeted at natural product molecules. Apart from this, current leadership strategies have led to a renewed interest in natural products in drug discovery. As a result, interest in natural products such as drug lead is rekindled, especially in dealing with antimicrobial resistance. We continue to attract readers' interest in acknowledging that a certain number of natural products/products are actually produced by bacteria and/or bacterial interactions with the "host where they have been set aside"; therefore, we consider this area of ​​natural product research should be greatly expanded. In the concluding section, we draw attention to the potential future indications of a natural product in drug design and development.