<p>To investigate whether <i>Akkermansia muciniphila</i> (<i>A. muciniphila</i>; AKK) affects colitis by regulating the ferroptosis signaling pathway, an mouse model of colitis was constructed, and the mice were administered with <i>A. muciniphila</i> and Erastin (ferroptosis agonist). HE staining and transmission electron microscopy were used to observe the pathological and microstructural changes of mouse colon tissues. The number of goblet cells was examined using alcian blue staining. The expression levels of indicators related to oxidative stress and ferroptosis were detected by ELISA, western blot and immunohistochemisty. Transcriptome and non-targeted metabolome sequencing were carried out to screen for the differentially expressed genes and metabolites. Immunofluorescence double staining was used to detect the co-localization of cell adhesion-related indicators.16S microbiota sequencing was performed on mouse feces. Erastin caused damage to colon tissues, decreased the expression of ZO-1 and E-Cadherin, and increased the expression of indicators related to oxidative stress and ferroptosis. The species-abundance was increased after <i>A. muciniphila</i> treatment, while it was decreased after treatment with <i>A. muciniphila</i> and Erastin. <i>A. muciniphila</i> reduced inflammatory cell infiltration, alleviated organelle damage, and decreased the number of goblet cells in mice with colitis. MDA, ROS, and Fe²⁺ levels in colitis tissues were increased, but they were decreased after <i>A. muciniphila</i> treatment. The expression of GPX4 and SLC7A11 was decreased, while ACSL4 was increased. <i>A. muciniphila</i> intervention reversed the trend of changes in the above indicators and enriched 19 pathways. In conclusion, <i>A. muciniphila</i> could treat colitis in mice, and its mechanism may be related to the inhibition of the ferroptosis signaling pathway.</p>