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CONTEXT It has been suggested that a gluten-free and casein-free (GFCF) diet may alleviate the symptoms of autism spectrum disorder (ASD) and facilitate neurodevelopment of children with ASD. Studies to date have been inconclusive. OBJECTIVE This study aimed to evaluate (through quantitative meta-analysis) the efficacy and safety of a GFCF diet for children with ASD. To our knowledge, this is the first time such an analysis has been carried out. DATA SOURCES Eight electronic databases were searched, from the establishment of each database up to March 27, 2020: PubMed, Web of Science, Embase (Ovid), PsycINFO (Ovid), Cochrane Library, CNKI, Wanfang, and VIP databases. DATA EXTRACTION Two authors independently performed the data extraction and risk-of-bias assessment. DATA ANALYSIS A quantitative meta-analysis was performed with standard procedures by using Stata SE 15 software. Within the total of 8 studies, with 297 participants, 5 studies reported significant reductions in stereotypical behaviors [standard mean difference (SMD) = -0.41, 95% confidence interval (CI): -0.68 to -0.15], and 3 studies reported improvements in cognition (SMD = -0.46, 95% CI: -0.91 to -0.01) following GFCF dietary intervention. No statistically significant changes were observed in other symptomatic categories (all P > 0.05). CONCLUSION The current meta-analysis showed that a GFCF diet can reduce stereotypical behaviors and improve the cognition of children with ASD. Though most of the included studies were single-blind, the benefits of a GFCF diet that have been indicated are promising. Additional studies on a larger scale are warranted. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42020177619.