Cockroaches are one of the hardiest insects that have survived on this planet for millions of years. They thrive in unhygienic environments, are able to survive without food for up to 30 days, without air for around 45 min and being submerged under water for 30 min. Cockroaches are omnivorous and feed on a variety of foods, including cellulose and plastic, to name a few. It is intriguing that cockroaches are able to endure and flourish under conditions that are harmful to
Homo sapiens
. Given the importance of the gut microbiome on its’ host physiology, we postulate that the cockroach gut microbiome and/or its metabolites, may be contributing to their “hardiness”, which should be utilized for the discovery of biologically
active molecules for the benefit of human health. Herein, we discuss the biology, diet/habitat of cockroaches, composition of gut microbiome, cellular senescence, and resistance to infectious diseases and cancer. Furthermore, current knowledge of the genome and epigenome of these remarkable species is considered. Being one of the most successful and diverse insects, as well as their extensive use in traditional and Chinese medicine, the lysates/extracts and gut microbial metabolites of cockroaches may offer a worthy resource for novel bioactive molecule(s) of therapeutic potential for the benefit of human health and may be potentially used as probiotics.