Background: This systematic review evaluates the efficacy and safety of Mycophenolate Mofetil (MMF) for managing treatment‐resistant Inflammatory Bowel Disease (IBD), emphasizing remission rates and adverse effects. Methods: Observational and controlled trials assessing MMF’s impact on IBD were included, excluding non-English and pediatric studies. Comprehensive searches were conducted in Embase, Medline/PubMed, Scopus, and Web of Science through October 2023. The risk of bias was evaluated using the NIH quality assessment tool, and results were synthesized using a random-effects meta-analysis model. Results: Twelve studies comprising 446 participants (333 with Crohn’s disease and 113 with ulcerative colitis) were analyzed. The meta-analysis revealed remission rates of 62.2% at 8 weeks and 52.8% at 6 months. Adverse effects occurred in 26.1% of patients, with nausea and vomiting being the most common. Treatment discontinuation due to failure and intolerance was observed in 29.7% and 20% of cases, respectively. Discussion: The findings suggest that MMF effectively induces remission in IBD patients unresponsive to conventional therapies, although a notable proportion experienced adverse events or treatment failure. Careful patient selection and monitoring are essential. Conclusion: MMF presents a promising alternative for managing resistant IBD, but its adverse effect profile warrants cautious application. Further research is needed to optimize dosing strategies and assess long-term outcomes in this challenging patient population. These results underscore the potential of MMF as an effective therapeutic option while emphasizing the importance of individualized treatment plans and rigorous clinical monitoring. Future studies should focus on long-term safety and dosing. Additional robust research is required.