Patients with refractory inflammatory bowel disease (IBD) face difficulty in the treatment strategy. Combined advanced targeted therapies may obtain higher therapeutic efficacy. However, few studies compare the efficacy and safety of dual biologic therapy (DBT) with biologic small-molecule therapy (BMT) for refractory IBD. We aimed to compare the effectiveness of DBT with BMT. We retrospectively analyzed the data of patients with refractory IBD treated with DBT (n = 22) or BMT (n = 21). The primary outcome was the clinical remission rate at week 12. Secondary outcomes included the clinical response rate, endoscopic response rate, endoscopic remission rate, colectomy rate, and rate of adverse events (AEs) at week 12. At week 12, the clinical remission rates in the DBT group and BMT group were 22.7% and 28.6%, respectively. No statistically significant difference was observed between the two groups (p = 0.661). There were also no statistically significant differences between the DBT group and BMT group in the clinical response rate (68.2% vs. 71.4%, p = 0.817), endoscopic response rate (66.7% vs. 68.8%, p = 1.000), endoscopic remission rate (4.8% vs. 18.8%, p = 0.296) and colectomy rate (4.5% vs. 23.8%, p = 0.167). Two patients (9.5%) in the BMT group and no patients in the DBT group experienced AEs. However, the difference was not statistically significant (p = 0.233). In conclusion, this study revealed that there may be similar effectiveness and safety of DBT and BMT for patients with refractory IBD. Further multi-center, prospective randomized controlled trials are necessary to confirm this conclusion.