Ustekinumab has two alternative drug maintenance intervals for inflammatory bowel disease (IBD), every 8 weeks (Q8W) and every 12 weeks (Q12W). The current study aimed at evaluating the comparative efficacy and safety of the two maintenance intervals in patients with IBD. A systematic search on PubMed, Web of Science, Cochrane Library, and EMBASE was carried out. The relative risk (RR) was pooled for efficacy and safety outcomes between the two intervals at various follow-up time points, categorized as short term (less than 44 weeks), medium term (about 92 weeks), and long term (about 152 weeks). A total of 14 studies with 1448 patients were included. Q8W didn’t result in a remarkably higher proportion of clinical remission compared to Q12W at short term (RR, 0.99; 95% CI, 0.83–1.16), medium term (RR, 1.05; 95% CI, 0.91–1.20), and long term (RR, 1.07; 95% CI, 0.91–1.26). Similarly, no substantial differences exist at short term in clinical response (RR, 1.00; 95% CI, 0.85–1.17), endoscopic remission (RR, 0.97; 95% CI, 0.26–3.69), and histologic improvement (RR, 1.13; 95% CI, 0.93–1.36) between the two intervals. For safety outcomes, the RR values for any adverse events in the short, medium, and long term were 1.10 (95% CI, 1.00–1.21), 1.14 (95% CI, 1.08–1.20), and 1.12 (95% CI, 1.07–1.17) for Q8W versus Q12W. Finally, we conclude that ustekinumab maintenance therapy administered every 8 and 12 weeks showed similar effectiveness in achieving efficacy outcomes in IBD patients, and most safety outcomes were significantly better for Q12W during the maintenance phase.