Background and aim Diagnosing inflammatory bowel disease (IBD), determining the appropriate treatment and follow-up of patients rely mainly on endoscopy and biopsy. Finding a sensitive, specific, cost-effective and less-invasive biomarker is the focus of much of the current research in this field. The aim was to investigate the relation between serum matrix metalloproteinase-9 (MMP-9) levels and disease activity in patients with IBD, correlating with clinical and endoscopic indices of disease activity and with treatment received. Patients and methods Sixty patients (30 with ulcerative colitis, 30 with Crohn’s disease) and 20 controls were included. Serum MMP-9 levels were measured for all patients and controls by ELISA. Clinical activity was determined by partial Mayo score for patients with ulcerative colitis and Crohn’s Disease Activity Index for patients with Crohn’s disease, and endoscopic activity was assessed using Ulcerative Colitis Endoscopic Index of Severity for patients with ulcerative colitis and Simple Endoscopic Score of Crohn’s disease for patients with Crohn’s disease. Results Serum MMP-9 was higher in patients with active ulcerative colitis than in patients with inactive disease and the control group. Serum MMP-9 was also higher in patients with active Crohn’s disease than in patients with inactive disease and the control group. In both ulcerative colitis and Crohn’s disease groups, there was a significant difference between serum MMP-9 levels in patients receiving conventional treatment and those on biological treatment, with lower levels of the marker detected in the sera of patients subgroups receiving biologics. Conclusion Serum MMP-9 can be used to differentiate between active and inactive IBD (including both ulcerative colitis and Crohn’s disease).