Background: Although the number of biological therapies for the treatment of Crohn’s disease (CD) is rapidly increasing, their efficacy in inducing healing of fistulas in perianal Crohn’s disease (pCD) is practically unknown, although they occur in up to 50% of patients with CD. Objective: We aimed to investigate the clinical effectiveness of ustekinumab for pCD in a systemic review and meta-analysis. Methods: Studies describing the efficacy of ustekinumab on fistulas in pCD in PubMed and EMBASE database from inception until 22 September 2020, were assessed in a systemic review and meta-analysis. The random-effect model was applied for the meta-analysis. Results: The systematic review of the current literature yielded 2,243 studies of which nine studies with a total of 396 patients were found eligible for inclusion. The pooled proportions of patients experiencing fistula response were 41.0% (95% CI 23.9–60.6%9), I ² = 85%, 39.7% (95% CI 24.3–57.4%), I ² = 69% and 55.9% (95% CI 40.8–69.9%, I ² = 67% at weeks 8, 24, and 52, respectively. Regarding fistula remission, the pooled proportions were 17.1% (95% CI 8.1–32.7%), I ² = 45%, 17.7% (95% CI 1.8–71.9%), I ² = 68%, and 16.7% (95% CI 3.0–56.5%, I ² = 51% at week 8, 24, and 52, respectively. Conclusion: In this systematic review with meta-analysis, we found a signal of efficacy of ustekinumab on fistulizing pCD, emphasizing that these patients might benefit from this therapy.