Mounting clinical and experimental evidence suggests the gut–brain interplay as a novel important paradigm in translational neuroscience, including the critical role for gut microbiota in modulating brain development and behavior, as well as neuroimmune and neuroendocrine responses. Animal models are an indispensable tool in studying the central nervous system (CNS) disorders and their mechanisms. Recently, the zebrafish (Danio rerio) has become a powerful new model organism in neuroscience, including studying the gut-brain axis. Here, we discuss zebrafish models of gut-brain interplay, endocrine and toxicological effects of zebrafish microbiota, and their impact on neuroimmune and behavioral processes. We particularly emphasize the growing utility of zebrafish models in gut-brain research, as they foster future discoveries of new interconnections between these systems.