Background/Aims: Disruptions in tight junction (TJ) protein expression leading to duodenal epithelial barrier impairment may contribute to increased intestinal permeability, potentially playing a role in functional dyspepsia (FD) pathophysiology. Currently published studies evaluated the role of several TJ proteins in FD patients with inconsistent results. Therefore, we conducted this systematic review and metaanalysis to evaluate the duodenal mucosal expression of several TJ proteins in FD. Methods: We performed a systematic electronic search on PubMed, EMBASE, and Scopus using predefined keywords. Diagnosis of FD by Rome III or Rome IV criteria was considered acceptable. Full articles satisfying our inclusion and exclusion criteria were included. The principal summary outcome was the mean difference of several TJ proteins in FD patients and control subjects. Results: A total of 8 and 5 studies were included in our qualitative and quantitative synthesis, respectively, with a total population of 666 participants, out of which 420 were FD patients. No significant differences were observed between FD patients and controls in the expression of claudin-1 (–0.102 [95% CI, –0.303, 0.099]), claudin-2 (0.161 [95% CI, –0.134, 0.456)], claudin-3 (0.278 [95% CI, –0.280, 0.837]), claudin-4 (0.045 [95% CI, –0.264, 0.354]), ZO-1 (–0.221 [95% CI, –0.683, 0.241]), ZO-2 (–0.070 [95% CI, –0.147,0.007]), ZO-3 (–0.129 [95% CI, –0.376, 0.118]), β-catenin (–0.135 [95% CI, –0.484, 0.214]), E-cadherin (–0.083 [95% CI, –0.229, 0.063]), and occludin (–0.158 [95% CI, –0.409, 0.093]). Conclusions The expressions of all evaluated proteins including claudin-1, claudin-2, claudin-3, claudin-4, ZO-1, ZO-2, ZO-3, β-catenin, E-cadherin, and occludin did not significantly differ between FD patients and controls. However, due to the limited number of included studies, results should be interpreted with caution.