Abstract Introduction/Objective Celiac disease (CD) is a long-term autoimmune disorder that affects individuals genetically predisposed to gluten intolerance. Biomarkers, particularly anti-tissue transglutaminase antibody (anti-tTG ab), are crucial in indicating disease states and have potential as non-invasive substitutes for mucosal biopsies in assessing the severity of intestinal damage. This study aims to systematically review and analyze the correlation between anti- tTG antibody levels and the severity of villous abnormalities in patients with celiac disease to evaluate the potential of anti-tTG as a non-invasive diagnostic tool. Methods/Case Report Following PRISMA guidelines, a comprehensive literature search selected 15 studies focusing on the correlation between anti-tTG antibodies and villous atrophy. Systematic data extraction and quality assessments were performed, followed by statistical analyses to determine the strength and consistency of associations. Results (if a Case Study enter NA) Analysis of data from four studies on anti-tTG antibody positivity revealed a nearly significant pooled effect size (p = 0.06) with considerable heterogeneity (I^2 = 97%, p < 0.00001). Additionally, data from five studies using the MARSH classification of histological damage, aggregated using a random-effects model, showed overall statistical significance (Z = 3.36, p = 0.0008). Conclusion Anti-tTG antibodies serve as a reliable indicator of villous damage in CD, supporting their dual utility in diagnosis and monitoring. High anti-tTG antibody titers could potentially eliminate the need for invasive biopsy procedures in certain patient subsets, underscoring the promise of more refined and non-invasive diagnostic approaches, although further research is needed to address the implications of high heterogeneity observed in the studies.