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Current diagnostic paradigms for Crohn’s disease (CD) activity assessment remain fragmented across imaging and laboratory modalities. This study seeks to investigate the diagnostic efficacy of intestinal computed tomography imaging combined with serum inflammatory markers in detecting active Crohn’s disease (CD). Data from 68 patients undergoing CT enterography (CTE) of the small intestine (43 patients with active CD and 25 controls) were analyzed. CTE findings, including plain CT values and enhanced ΔCT values, as well as neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and platelet-to-albumin ratio (PAR), were collected. The correlations between these indicators and CD activity were also explored. Logistic regression and receiver operating characteristic curve (ROC) analyses were conducted to evaluate the diagnostic value of individual and combined markers for active CD. Significant differences in CTE imaging features and serum optimization indices were observed between cases with mild to moderate active CD and controls (P < 0.05). The area under the curve of CTE imaging (venous phase ΔCT value (0.896)) and serum indices (NLR (0.902)) in predicting CD were the highest in the moderately active stage. The area under the curve of the combination of the indices (intestinal wall thickness, enhanced ΔCT value, NLR, PLR, and CAR) was 0.947. Among them, NLR, PLR, and CAR exhibited the highest sensitivity (95.0%), whereas enhanced arterial phase ΔCT value demonstrated a higher specificity (93.8%). Venous-phase ΔCT values and NLR were identified as significant predictors of moderately active CD. Additionally, serum optimization indices were strongly correlated with CTE images (P < 0.01). CTE imaging features and serological optimization indicators can serve as potential noninvasive markers for diagnosing active CD, and higher diagnostic value can be achieved through combined assessments. Venous-phase ΔCT values and the NLR are promising markers of moderately active CD.