Background: Published research findings regarding the relationship between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the risk of preeclampsia (PE) have generated conflicting results. A meta-analysis was conducted to investigate whether the MTHFR A1298C polymorphism is associated with preeclampsia. Methods: We conducted a systematic search across several databases, including PubMed, Embase, Web of science, China National Knowledge Infrastructure, and Chinese Biomedicine Databases, to identify relevant studies. We then calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) to assess the association between the MTHFR A1298C polymorphism and preeclampsia (PE) risk. Results: A total of 11 studies were enrolled in this meta-analysis. The pooled analyses revealed that MTHFR A1298C polymorphism significantly decreased the risk of PE (allele contrast (A (alanine) vs. C (glutamate) ): OR, 0.81; 95% CI, 0.71–0.93, p = 0.207; homozygote (AA vs. CC): OR, 0.57; 95% CI, 0.40–0.79, p = 0.056; heterozygote (AC vs. CC): OR, 0.62; 95% CI, 0.45–0.87, p = 0.010; dominant model (AA + AC vs. CC): OR, 0.59; 95% CI, 0.43–0.81, p = 0.031; recessive model (AA vs. AC + CC): OR, 0.83; 95% CI, 0.70–0.98), p = 0.817. Conclusion: Present meta-analysis reveals that MTHFR A1298C variant may serve as genetic biomarkers of PE. The study was registered on PROSPERO (https://www.crd.york.ac.uk/prospero/), registration number: CRD42023459681.