Objective: There is still an unmet need for a reliable and straightforward biomarker to diagnose and monitor cow’s milk protein allergy (CMPA). Fecal calprotectin (FC) has been reported as a biomarker for CMPA. Therefore, the meta-analysis aimed to evaluate the value of FC in the diagnosis and monitoring of CMPA. Methods: PubMed, EMBASE, and the Cochrane Library up to April 2022 were searched for relevant studies. Pooled standardized mean difference (SMD) and 95% confidence intervals (CIs) were determined using the forest plot. Heterogeneity was used to determine the fixed or random-effect model. Results: Twelve studies including 310 patients and 217 controls were available for the meta-analysis. The FC levels in children with CMPA were significantly higher than in healthy control (SMD = 1.15; 95% CI: 0.38–1.91). After elimination diet treatment, FC levels were reduced considerably with the pooled SMD of 0.87 (95% CI: 0.48–1.26). Conclusion: The results indicated that FC could be a simple and reliable biomarker for diagnosing CMPA, especially in non-IgE-mediated CMPA infants. Besides, calprotectin was also potential for predicting therapy response of CMPA.