This meta-analysis has been conducted to compare ustekinumab and adalimumab as induction or maintenance therapy in patients with moderate to severe Crohn's disease (CD). The current meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two investigators independently searched online databases including PubMed, Cumulated Index to Nursing and Allied Health Literature (CINAHL), and Cochrane Library for relevant articles published up to April 2023. The initial search terms were “ustekinumab,” “adalimumab,” and “Crohn’s disease". Three studies (with a total of 612 patients) were included in the present meta-analysis. We did not find any significant difference in clinical remission (OR: 1.31, 95% CI: 0.68-2.52), clinical response (OR: 1.39, 95% CI: 0.39-4.91), endoscopic remission (OR: 1.56, 95% CI: 0.66-3.64), and steroid-free remission (OR: 0.98, 95% CI: 0.67-1.42) between patients who received ustekinumab and patients who received adalimumab. In conclusion, this meta-analysis provides valuable insights into the efficacy and safety of ustekinumab and adalimumab in the treatment of moderate to severe CD. Our findings indicate that both drugs have similar effectiveness in achieving clinical remission, clinical response, radiological remission and steroid-free remission.