BACKGROUND: Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by relapsing and remitting inflammation of the gastrointestinal tract. Reliable and non-invasive methods to assess disease activity are crucial for guiding treatment and improving patient outcomes. This study investigates how intestinal ultrasound (IUS) parameters and fecal calprotectin (FC) levels correlate with endoscopic severity scores in Crohn's disease (CD). AIM AND OBJECTIVE: To assess the effectiveness of IUS as a complementary tool to conventional methods in predicting disease severity in CD by correlating IUS parameters, specifically bowel wall thickness (BWT) and color Doppler flow (CDF), with FC levels and Simple Endoscopic Score for Crohn's Disease (SES-CD). MATERIALS AND METHODS: A cross-sectional observational study was conducted on 45 patients with confirmed CD at the Department of Gastroenterology. Clinical data, FC levels, SES-CD scores, and IUS measurements were collected and analyzed. The correlation between BWT, FC, and SES-CD scores was assessed using Pearson correlation, and the sensitivity and specificity of combined IUS and FC parameters were calculated. RESULTS: The study found significant correlations between higher CDF scores and increased FC levels in the ileum (P = 0.002) and ascending colon (P < 0.001). BWT showed a significant positive correlation with SES-CD in the descending colon (r = 0.440, P = 0.003) and rectosigmoid (r = 0.366, P = 0.014). The combination of BWT > 3 mm and FC > 250 microg/g demonstrated high sensitivity and specificity, particularly in the ileum (sensitivity 88.6%, specificity 78.9%) and descending colon (sensitivity 80.9%, specificity 87.7%). CONCLUSION: Combining IUS parameters, particularly BWT and CDF, with FC levels provides a robust method for predicting disease severity in CD. This approach can enhance disease monitoring, reduce reliance on invasive procedures, and improve patient management in clinical practice.