Coculture systems (CCSs) are experimental tools used to study the interactions of anaerobic bacteria among themselves and the gut epithelial cells under conditions simulating the human gut, unlike those in animal models. Although the studies on animal models are useful in determining the relationship between the causative agents of infections and human infections, they have disadvantages, such as ethical issues, in addition to the differences in the microbiota of the animal and humans. Therefore, the results obtained using animal models cannot be directly extrapolated to humans. CCSs can more completely reflect in vivo gut homeostasis and contribute to better understanding of the interplay between the intestinal cells and anaerobes, prevalent among the gut bacteria. Moreover, they provide new insights on the pathogenesis of infections and aid in assessing the usefulness of new probiotics and antibacterials. Therefore, CCSs, including the gut-on-a-chip models, can significantly improve microbiota-based therapy. Moreover, they can also be used to detect microbiota-derived metabolites such as those with mutagenic properties. The aim of this review was to explore selected CCS models of anaerobes with intestinal epithelium and their application in investigating intestinal homeostasis. The focus was to highlight the application of different CCSs and important data obtained from their implementation.