Background: Congenital heart disease (CHD) is a leading cause of neonatal morbidity and mortality , whose underlying pathogenesis remains largely unclear, and lacks reliable biomarkers or therapeutic targets during pregnancy . This study aimed to explore the role of the peptide ELABELA (ELA) in the development of fetal CHD and evaluate its potential as a biomarker and therapeutic target. Methods: ELA levels were analyzed in human heart with CHD and plasma from pregnancies affected by fetal CHD using quantitative PCR, immunofluorescent staining, and enzyme immunoassays. Mouse models with cardiac-specific ELA deletion were utilized to investigate the impact of ELA on cardiac development. Single-cell RNA sequencing and mitochondrial function assay were conducted to investigate downstream mechanisms. Exogenous ELA was administered to evaluate its therapeutic effects in mouse models. And its potential role to screen for fetal CHD during pregnancy was explored in large cohort studies using ELISA. Results: ELA levels are significantly reduced in human fetal cardiac tissues with CHD and in maternal plasma during pregnancies with fetal CHD. In mice, ELA deletion in cardiac progenitor cells disrupted mitochondrial function, and induced mitochondrial swelling by disrupting the APJ-AKT-BCL2/BAX axis, leading to cardiac malformations. Administration of exogenous ELA notably reduced both CHD severity and incidence in mice. Conclusions: This study identifies ELA as a crucial regulator of fetal cardiac development and mitochondrial homeostasis, while exogenous ELA administration demonstrates therapeutic potential. These findings underscore the value of ELA as a novel biomarker and therapeutic target for the prevention and management of fetal CHD during gestation.