Berberine is a promising agent for modulating the intestinal microbiota, playing a crucial role in human health homeostasis. This natural compound promotes the growth of beneficial bacteria such as , , and while reducing harmful bacteria such as . Clinical and preclinical studies demonstrate that Berberine helps regulate T2D and metabolic disorders, improves blood glucose levels during T2D, and reduces lipid profile and chronic inflammation, especially when combined with probiotics. Berberine represents a promising adjuvant therapy for inflammatory diseases, particularly intestinal disorders, due to its multifaceted actions of inhibiting proinflammatory cytokines and pathways during IBS, IBD, and UC and its modulation of gut microbiota and/or enhancement of the integrity of the intestinal epithelial barrier. This review establishes the basis for future treatment protocols with berberine and fully elucidates its mechanisms.