Crohn's disease (CD) and ulcerative colitis (UC) are two forms of inflammatory bowel disease (IBD). This chronic, immune-mediated disorder leads to inflammation in specific gastrointestinal tract regions. Myocarditis is a rare but significant IBD complication that affects roughly 0.3% of cases. Mesalazine-induced myocarditis is a rare side effect of mesalazine therapy, which is considered a standard treatment for IBD. Increased mortality and cardiogenic shock are possible outcomes of this adverse response. The objectives of this study are to characterize the clinical features of mesalazine-induced myocarditis in patients with IBD, to conduct a comprehensive analysis of mesalazine-related myocarditis cases in IBD patients, to review the existing literature, to elucidate the pathophysiological mechanisms of myocarditis in IBD, and to determine whether myocarditis represents an extraintestinal manifestation of IBD or an adverse drug reaction to mesalazine. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Relevant literature was retrieved from Cochrane, ScienceDirect, Google Scholar, PubMed, and PubMed Central (PMC). Only articles published in English or with a full English translation available within the last 10 years (2014-2024) were included. A rigorous quality assessment tool was applied to ensure the quality of evidence-based medicine that will be utilized to construct a conclusion and direct future reviews. Among 43 patients analyzed, 29 (67%) developed myocarditis attributable to mesalazine treatment, while 14 (33%) exhibited myocarditis unrelated to the medication. Our findings indicate that myocarditis in IBD is more likely to be a severe drug reaction than an extraintestinal manifestation of IBD progression. In drug-induced myocarditis cases, mesalazine derivatives, including sulfasalazine, mesalamine, and balsalazide, were most frequently implicated. Potential mechanisms underlying mesalazine-associated myocarditis include IgE-mediated hypersensitivity reactions, direct cardiotoxicity, cell-mediated hypersensitivity, or humoral antibody responses to drug metabolites. When treating myocarditis in IBD, whether due to medication or as an extraintestinal manifestation, discontinuing the offending drug and initiating immunosuppressive therapy appear to be the most effective approach.