Background and objective <p>Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis (UC), are chronic conditions characterized by intestinal inflammation. Soluble fiber is fermented by gut microbiota into short-chain fatty acids (SCFA), which possess anti-inflammatory properties. This review aimed to assess the efficacy of oral and topical SCFA administration in patients with UC.</p> Methods <p>A systematic review with meta-analysis was conducted in accordance with PRISMA guidelines. Meta-analyses were performed using means and standard deviations to assess clinical and histological outcomes. Endoscopic criteria were also evaluated to determine the effectiveness of the intervention.</p> Results <p>Nine studies compared SCFA supplementation with standard therapy, and one employed a crossover design. Oral SCFA, when combined with standard treatment, as associated with reductions in fecal calprotectin and C-reactive protein levels. Meta-analyses of topical SCFA administration revealed a standardized mean difference of − 0.29 ± 0.22, (95% CI: − 0.65 to 0.07; heterogeneity I² = 28%) for the Ulcerative Colitis Disease Activity Index score, and − 0.73 ± 0.61, (95% CI: − 1.58, 0.12; heterogeneity I² = 64%) for histological scores. Endoscopic scores decreased in both intervention and control groups. No adverse effects were observed.</p> Conclusion <p>SCFA administration, either orally or topically, has been investigated as a potential adjunct to standard UC therapies. However, the current evidence is limited, particularly for oral administration, which has only been assessed in two studies. Further research is needed to clarify the potential role of SCFA administration.</p>