Mental well-being and brain health are increasingly seen as a consequence of holistic physiological homeostasis that includes not only the brain but also peripheral organs. The gut, also sometimes referred to as the second brain, has significant impacts on how we think and feel. It has been increasingly accepted that the gut is also a conduit for neurological diseases and psychological disorders. As such, it is important to understand the mechanisms underlying gut-brain communication and how modern medicine and nutrition could modulate this signaling pathway. In the past, animal models dominated this field of research. With the recent advancements in microfluidics and cell culture methodologies, there have been increasing number of multi-organ models or organ-on-a-chip models that attempt to mimic the complexity of gut-brain axis in vitro. These models minimally include gut and brain components but also contains microbiome and blood brain barriers. The increasing complexity of the models rise out of the need to isolate the physiological system that critically regulate this important communication pathway to advance our understanding of the mode of action for drugs or natural bioactives. Therefore, this collection summarizes the methodological advancements in these gut-brain axis in a dish as well as animal models of gut-brain axis to compare and highlight the key preclinical models that are currently available or in development.