Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia, which poses a serious threat to human health. Moringa oleifera Lam. is a medicinal and edible plant with various physiological functions. However, its main hypoglycemic components and mechanisms are still unclear. In this study, network pharmacology and bioinformatics were used to analyze the potential bioactive substances of M. oleifera leaf extract (MOLE) and its hypoglycemic mechanism. Studies have shown that MOLE has the effect of increasing glucose consumption in insulin resistant-HepG2 cells. MOLE was found to contain 975 compounds by ultrahigh performance liquid chromatography-mass spectrometry (UHPLC-MS). Network pharmacology analysis indicated that the main active component was robinetin and the identified core genes were AKT1 and GAPDH. KEGG pathway enrichment analysis showed that the hypoglycemic effect of MOLE may be closely related to the PI3K-Akt signaling pathway. This study revealed the possible active components and mechanisms of action of M. oleifera for hypoglycemia, laying the theoretical foundation for subsequent studies.