Mindfulness-based interventions have shown some efficacy in decreasing stress levels and improving quality of life. However, so far, only a few studies have studied this type of intervention among patients with inflammatory bowel disease and none of them have studied their effects on inflammatory biomarkers. This current study was a two-armed, single-centre, randomised (2:1 ratio) controlled trial used to evaluate the effects of a mindfulness-based intervention (n = 37) compared to standard medical therapy (n = 20) in patients with Crohn's disease or ulcerative colitis. The mindfulness intervention blended four internet-based therapy modules with four face-to-face support sessions. The outcomes we assessed were faecal calprotectin (primary outcome), C-reactive protein, and cortisol levels measured in hair samples at several timepoints. The between-group analysis highlighted significant decreases in faecal calprotectin and in C-reactive protein levels in the mindfulness-based intervention group compared to the standard medical therapy group at the six-month follow-up (faecal calprotectin: -367, [95% CI: -705, -29], P = 0.03; C-reactive protein: -2.82, [95% CI: -5.70, 0.08], P = 0.05), with moderate to large effect sizes (faecal calprotectin: ηp2 = 0.085; C-reactive protein: ηp2 = 0.066). We concluded that mindfulness-based therapy administered as part of standard clinical practice effectively improves inflammatory biomarkers in patients diagnosed with inflammatory bowel disease.