Mucus is a viscoelastic hydrogel that lines and protects the epithelial surfaces of the body that houses commensal microbiota and functions in host defense against pathogen invasion. As a first‐line physical and biochemical barrier, intestinal mucus is involved in immune surveillance and spatial organization of the microbiome, while dysfunction of the gut mucus barrier is implicated in several diseases. Mucus can be collected from a variety of mammalian sources for study, however, established methods are challenging in terms of scale and efficiency, as well as with regard to rheological similarity to native human mucus. Therefore, there is a need for mucus‐mimetic hydrogels that more accurately reflect the physical and chemical profile of the in vivo human epithelial environment to enable the investigation of the role of mucus in human disease and interactions with the intestinal microbiome. This review will evaluate the material properties of synthetic mucus mimics to date designed to address the above need, with a focus toward an improved understanding of the biochemical and immunological functions of these biopolymers related to utility for research and therapeutic applications.