Unbalanced mitochondrial dynamics exacerbates inflammation and is of interest for its possible role in the pathogenesis of inflammatory bowel disease (IBD). The current study utilized the P110 peptide drug, a selective inhibitor of mitochondrial fission, to investigate the relationship between mitochondrial dynamics and colitis. First, the functionality of the P110 peptide was verified in T84 colon epithelial cells in response to carbonyl cyanide m-chlorophenyl hydrazine (CCCP), a mitochondrial stressor. Second, the therapeutic potential of the P110 peptide was tested in a mouse model of IBD, chemically induced by dextran sodium sulfate (DSS). Treatment with P110 was found to reduce macroscopic symptoms of colitis and provides evidence that aberrant mitochondrial dynamics contribute to IBD. The results provide motivation for further investigation into the specific mechanisms by which mitochondrial dynamics impact IBD and a possible new therapeutic target for the treatment of IBD.