In recent years, the holistic view is becoming the dominant perspective for the resolution of medical issues. Metabolomic approaches offer new opportunities to enhance our understanding of fetal biology and the multifactorial impact of perinatal diseases. Although metabolomics in maternal-fetal biology is increasing, it is not yet widely applied in perinatal medicine. Our group has been at the forefront of applying these powerful approaches to understanding pregnancy and fetoplacental development. This review shows our experience about metabolomics studies utilizing chorionic villus and amniocentesis samples obtained in our busy prenatal diagnostic center in Cagliari, Sardinia. The findings suggest that metabolomic approach in perinatal medicine could be helpful in establishing placental/fetal maturity, diagnosing aneuploidy, or identifying early placental dysfunction. Although omics approaches and the network analysis in perinatal physiology hold promise for a new generation of prenatal biomarkers and potential therapeutics, further investigation is need to improve our knowledge and our ability to diagnose and treat diseases of pregnancy.