The development of novel bioactive molecules is urgently needed, especially with increasing fatalities occurring due to infections by bacteria and escalating numbers of multiple-drug-resistant bacteria. Several lines of evidence show that the gut microbiome of cockroaches, snakes, crocodiles, water monitor lizards, and other species may possess molecules that are bioactive. As these animals are routinely exposed to a variety of microorganisms in their natural environments, it is likely that they have developed methods to counter these microbes, which may be a contributing factor in their persistence on the planet for millions of years. In addition to the immune system, the gut microbiota of a host may thwart colonization of the gastro-intestine by pathogenic and/or foreign microorganisms through two mechanisms: (i) production of molecules with antibacterial potential targeting foreign microorganisms, or (ii) production of molecules that trigger host immunity targeting foreign microorganisms that penetrate the host. Herein, we discuss and deliberate on the current literature examining antibacterial activities that stem from the gut bacteria of animals such as crocodiles, cockroaches, and water monitor lizards, amongst other interesting species, which likely encounter a plethora of microorganisms in their natural environments. The overall aim is to unveil a potential library of novel bioactive molecules for the benefit of human health and for utilization against infectious diseases.