Vitamin and homocysteine (Hcy) alternations have been associated with psychiatric disorders. The aim of this meta-analysis was to assess the association of serum vitamin and Hcy levels with obsessive-compulsive disorder (OCD). Following PRISMA protocol, we used the databases including Scopus, PubMed, Google Scholar, and Web of Science with no time restriction. Data were pooled using a random-effects model and/or fixed-effects model to estimate the standard mean difference (SMD) for evaluation of the strength of association analyses. Our data showed a significant reduction in vitamin B-12 (SMD = -0.58, 95% CI = -1.08 to -0.08, p = 0.02, I-2 = 65%; p(heterogeneity) = 0.06), vitamin E (SMD = -0.89, 95% CI = -1.23 to -0.56, p < 0.00001, I-2 = 23%; p(heterogeneity) = 0.26), and vitamin C (SMD = -1.40, 95% CI = -2.44 to -0.36, p = 0.008, I-2 = 92%; p(heterogeneity) < 0.0001) in OCD patients. In addition, the findings showed significantly higher levels of Hcy (SMD = 1.11, 95% CI = [0.48, 1.75], p = 0.0006, I-2 = 73%; p(h) = 0.02) in patients compared to controls. Also, our data showed that vitamin B-9 and D levels are not associated with OCD (vitamin B-9: SMD = -0.23, 95% CI = -1.01 to 0.55, p = 0.56, I-2 = 88%; p(heterogeneity) < 0.0001; vitamin D: SMD = -0.63, 95% CI = -1.41 to 0.15, p = 0.11, I-2 = 88%; p(heterogeneity) = 0.0002). Our findings support significant impacts of Hcy and vitamin B-12, E, and C levels in OCD pathogenesis. This will be important for prevention and treatment of OCD. However, further studies are recommended to elucidate more accurate conclusions.