Intestinal fucosylation, the enzymatic addition of fucose to glycoconjugates, represents a pivotal regulatory mechanism that modulates host–microbiota crosstalk in the gastrointestinal tract. This review comprehensively synthesizes current advances in the molecular mechanisms, multilevel regulatory networks, and functional implications of intestinal mucosal fucosylation. This review focuses on α(1,2)-fucosylation catalyzed by fucosyltransferase 2 (FUT2)—a reaction that determines the secretor status and modifies critical glycoconjugates, including mucins and human milk oligosaccharides. This review examines the dynamic regulation of epithelial fucosylation by host-derived factors—including immune mediators [notably interleukin-22 (IL-22) secreted by group 3 innate lymphoid cells (ILC3s)], the enteric nervous system (ENS), and microbial signals. Furthermore, this review details how fucosylated glycans shape the gut microbial ecosystem by serving as selective nutrient sources for beneficial symbionts—including Bifidobacterium and Bacteroides species—while concurrently enhancing colonization resistance against enteric pathogens. Dysregulation of this axis is increasingly associated with a spectrum of human pathologies, including inflammatory bowel disease (IBD), metabolic dysfunction, and enteric infections. Finally, this review discusses emerging therapeutic strategies targeting the modulation of intestinal fucosylation and its downstream physiological consequences, with particular emphasis on personalized approaches informed by host genetic determinants—most notably FUT2 secretor status.