Abstract Aim Perianal fistula (PAF) is a common condition encountered in surgical and gastroenterological practice. Distinguishing between cryptoglandular disease (CGD) and inflammatory bowel disease (IBD)‐related perianal disease is critical to ensure appropriate management. Faecal calprotectin (FC) has emerged as a promising non‐invasive biomarker for IBD; however, its role in acute perianal disease is not well established. This systematic review aimed to evaluate the diagnostic accuracy of FC in distinguishing IBD‐related perianal disease from CGD. Method A systematic literature search was conducted in PubMed, Embase and Cochrane databases following PRISMA guidelines. Studies were included if they assessed FC levels in patients with PAF and provided diagnostic accuracy metrics. Data extraction focused on study design, population characteristics, FC cut‐off values, sensitivity, specificity and area under the curve (AUC) metrics. Results Three studies met the inclusion criteria, all reporting significantly higher FC levels in IBD‐related PAF compared to CGD‐related fistulas. The proposed FC cut‐off values varied, ranging from 110 μg/g to 344 μg/g, with corresponding sensitivities between 52% and 81%, as well as specificities between 77% and 93%. The AUC values indicated moderate to high diagnostic accuracy. Conclusion FC shows potential as a diagnostic tool for differentiating IBD‐related perianal disease from CGD. A cut‐off of 110–150 μg/g appears most suitable for early screening, whereas a higher threshold may be appropriate for confirmatory diagnosis. Further prospective studies with standardized protocols are necessary to refine these thresholds and validate FC as a clinical decision‐making tool.