Antibiotic resistance has emerged due to the extensive, and at times irrational, use of antibiotics. Advances in genetics, biochemistry and chemical engineering in the past decades have unveiled this treasure trove of natural products (also called natural medicines) and allowed for their use against a variety of microbial infections to extend life and health, of all the diseases diagnosed, infectious diseases are of major concern due to the role of antibiotics in their prevention and cure. Since the discovery of the first antibiotic, penicillin different classes of antibiotics have been isolated and utilized in the clinic leading to remarkable achievement in the treatment of human and animal pathogens. The use of antibiotics, however, has not been restricted only to combat infectious diseases. They have also been used as drugs to treat tumors, viral infections, protozoa infections, trypanosomiasis and wounds. Microbiome-regulating natural products leverage the complexity of microbial communities, particularly the mammalian microbiome, in order to confer health benefits even without requiring direct activity against any potential human pathogens. These interventions can range from focusing on enhancing the presence of beneficial microbes – even to a certain defined community composition, to even targeting the vital growth and/or metabolic processes of disease-causing pathogens.