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Background Toxoplasma gondii (T. gondii) is an obligate intracellular opportunistic parasite that is the causative agent of toxoplasmosis. This parasite accounts for mental disorders; however, the relationship between T. gondii infection and depressive disorder is unclear. Regarding this, the present systematic review and meta-analysis was conducted to investigate the scientific evidence regarding the potential association between major depression disorder (MDD) and Toxoplasma infection. Methods For the purpose of the study, the articles related to the subject of interest were systematically searched in seven electronic databases. Special attention was given to the studies examining T. gondii seropositivity level in depressed patients and controls. Results The search process resulted in the identification of a total of 30 publications meeting the inclusion criteria and published up to April 2018 for the systematic review. Furthermore, 29 studies met the inclusion criteria to be entered into meta-analysis. Our meta-analysis involved the review of cross-sectional studies including 1657 depressed patients and 19565 individuals as controls and case-control studies entailing 1311 depressed cases and 6015 controls without depression. 1582 depressed people participated in cross-sectional studies whose results were reported as odds ratio (OR). In addition, the total number of participants was 15068 in this type of studies. Statistical analysis indicated that the pooled OR of the risk of anti-T. gondii IgG antibody in depressed individuals in case-control and cross-sectional studies was 1.15 (95% confidence interval (CI): 0.95-1.39). Conclusions As the findings of the reviewed articles indicated, toxoplasmosis is not a risk factor for MDD. However, it is necessary to perform further research to clarify the detailed association between T. gondii and dysthymia or mild and moderate depression. Furthermore, it is recommended to better investigate the effect of antibody titers on the relationship between depression and T. gondii infection.