Background and Objectives: Lipidomics is a pivotal tool for investigating the pathogenesis of mental disorders. However, studies qualitatively and quantitatively analyzing peripheral lipids in adult patients with schizophrenia (SCZ) and major depressive disorder (MDD) are limited. Moreover, there are no studies comparing the lipid profiles in these patient populations. Materials and Method: Lipidomic data for plasma samples from sex- and age-matched patients with SCZ or MDD and healthy controls (HC) were obtained and analyzed by liquid chromatography-mass spectrometry (LC-MS). Results: We observed changes in lipid composition in patients with MDD and SCZ, with more significant alterations in those with SCZ. In addition, a potential diagnostic panel comprising 103 lipid species and another diagnostic panel comprising 111 lipid species could distinguish SCZ from HC (AUC = 0.953) or SCZ from MDD (AUC = 0.920) were identified, respectively. Conclusions: This study provides an increased understanding of dysfunctional lipid composition in the plasma of adult patients with SCZ or MDD, which may lay the foundation for identifying novel clinical diagnostic methods for these disorders.