PURPOSE: Previous small-sample study suggested that fecal calprotectin (FC) combined with blood inflammatory biomarkers may aid in Crohn's disease (CD) diagnosis. This study aimed to validate the FC's diagnostic and mucosal healing assessment value of FC and a noninvasive composite index in pediatric CD. PATIENTS AND METHODS: Patients aged 2-17 years who underwent ileocolonoscopy for suspected or established CD were enrolled. Based on endoscopy, participants were classified into three groups: controls (functional gastrointestinal disorders), MH (mucosal healing, SES-CD <3, indicating minimal or absent visible inflammation), and ML (mucosal lesions, SES-CD ≥3). Fecal and blood samples were collected before endoscopy. Group differences were assessed using Kruskal-Wallis/Dunn's tests; correlations were evaluated via Spearman coefficients; ROC analysis was used to assess diagnostic performance. A composite index was constructed by weighting CRP, ESR, and IL-6 based on their correlations with FC. RESULTS: Among 123 participants, FC levels significantly differed across groups (P < 0.001), highest in patients with mucosal lesions. For distinguishing CD from controls, FC showed limited accuracy (AUC = 0.651), while the composite index improved performance (AUC = 0.754). In established CD, FC alone showed strong ability to differentiate mucosal healing from active disease (AUC = 0.888), with a slight improvement using the composite index (AUC = 0.921). CONCLUSION: The composite index integrating FC with inflammatory markers improves diagnostic performance over FC alone for distinguishing CD from controls and slightly enhances mucosal healing assessment, supporting its potential utility as a practical noninvasive tool for clinical monitoring in pediatric CD.