Inflammatory bowel disease (IBD) is a serious illness that negatively affects the human health due to its chronic course and serious complications. Glucagon like peptide (GLP-1) and its degradation enzyme inhibitor; dipeptidyl peptidase (DPP)-IV inhibitor, are used primarily as anti-diabetic drugs in patients with type 2 diabetes mellitus. However, current evidence suggests that both; GLP-1 (e.g. liraglutide) and the DPP-IV inhibitor (e.g. sitagliptin) may have a potential anti-inflammatory effect on various organ systems. This study was aimed to evaluate the potential of liraglutide and sitagliptin to improve colitis induced experimentally in mice using intra-rectal acetic acid, in comparison with sulfasalazine. Intra-rectal acetic acid was used to induce colitis in mice. The degree of inflammation was assessed using disease activity index, histopathological scoring, colonic length measurement as well as the colonic tissue expression of: the transcription factor; nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα), the oxidative stress marker; malondialdehyde and the inflammatory parameter; C-reactive protein. Moreover, random blood glucose was measured to ensure the safety of the tested drugs. Our results showed the positive impact of both liraglutide and sitagliptin on the assessed inflammatory parameters and their tolerability compared with sulfasalazine. Further clinical studies are needed to investigate the possibility to consider GLP axis as therapeutic adjuvants for IBD in the future.