Introduction: Isotretinoin is widely used in the treatment of moderate to severe acne vulgaris due to its proven efficacy. However, the use of this medication is associated with several adverse effects, including gastrointestinal symptoms. The possible association with inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis remains a subject of debate. Methods: A systematic review of the literature was performed in the PubMed, Embase and Cochrane Library databases, covering studies published from 2000 to 2024. The inclusion criteria considered randomized clinical trials, cohort studies, case-control studies and systematic reviews that reported gastrointestinal adverse effects related to the use of isotretinoin. The assessment of methodological quality was performed using the GRADE system, and the data were extracted independently by two reviewers. Results: The review found that mild gastrointestinal side effects, such as abdominal pain, nausea, and dyspepsia, are relatively common during isotretinoin treatment and tend to be transient and manageable. The association with inflammatory bowel disease remains unclear, with some studies indicating an increased risk, while others found no significant correlation. Risk factors such as high dose, prolonged duration of treatment, and history of previous gastrointestinal disease were associated with an increased likelihood of adverse effects. Conclusion: Although isotretinoin remains an effective treatment for acne vulgaris, its use should be accompanied by close monitoring, especially in patients with identified risk factors. A personalized approach is essential to maximize benefits and minimize risks. Future research should focus on identifying predictive risk factors to optimize treatment safety.