Congenital heart defects (CHDs) represent a significant burden of neonatal morbidity and mortality worldwide. Maternal biomarkers related to homocysteine and methionine metabolism have emerged as potential indicators of CHD risk during pregnancy. This review examines the current literature surrounding maternal biomarkers such as homocysteine, methionine, and related metabolites in the context of CHD development. Various studies investigating the association between abnormal levels of these biomarkers and the risk of CHDs are critically evaluated. Additionally, the underlying mechanisms linking aberrant homocysteine and methionine metabolism to CHD pathogenesis are discussed. Understanding the role of maternal biomarkers in CHD risk assessment holds promise for early detection, intervention, and prevention strategies to mitigate the impact of CHDs on neonatal health.