In the healthy gut mucosa, epithelial cells lining the lumen experience low oxygen levels, typically less than 2%, referred to as physiological hypoxia or physioxia. This gradient is maintained by the diffusion of oxygen from blood vessels along the crypt-villus axis, creating varying degrees of hypoxia within the mucosal lining. Physiological hypoxia at the mucosal surface regulates innate immunity by enhancing epithelial barrier function and modulating resident immune cells. However, studies suggest that mucosal inflammatory diseases involve hypoxia, exacerbated by increased oxygen consumption due to inflammatory cell influx, termed inflammatory hypoxia. Additionally, endothelial dysfunction may induce microvascular occlusion and thrombosis, further exacerbating tissue hypoxia. The human Gastrointestinal (GI) tract harbors a diverse community of microorganisms known as gut microbiota, pivotal in intestinal immunity and metabolism. Crucially, the microbiota contributes to maintaining a physiologically low oxygen environment in the gut, crucial for mucosal defenses. Dysbiosis of gut microbiota has been implicated in the pathogenesis of various inflammatory diseases and infections. This review aims to consolidate our current knowledge of the intricate interplay between inflammatory hypoxia and gut microbiota, emphasizing the pivotal roles of gut microbiota in the pathological hypoxic conditions observed in Inflammatory Bowel Disease (IBD).