Objective: To explore the active compounds and integrative mechanism of Moringa oleifera leaves in the treatment of hyperlipidemia based on network pharmacology. Methods: The chemical components of Moringa oleifera leaves were obtained through literature mining and CNKI. Hyperlipidemia targets were obtained via Gencards, OMIM, and DrugBank and protein interaction analysis was carried out by String. Metascape was used to perform GO and KEGG analysis. Finally, the molecular docking was performed by AutoDock Vina; experimental validation was performed by MTT, oil red O staining, and qRT-PCR on 3T3-L1 cells. Results: The core ingredients of Moringa oleifera leaves were sinapinic acid, palmitic acid, naringenin, etc. The core targets were ALB, TNF, PPARG, PPARA, VEGFA, etc. The signaling pathways included AGE-RAGE and PPAR signaling pathway, lipid, and atherosclerosis, etc. The molecular docking indicated strong binding activities. The experiments of 3T3-L1 cells showed that the toxicity of flavonoids to cells was significant at high concentrations (50-100 μmol/L), the fat content decreased by 8.45%, 16.28%, and 31.33%, respectively, after the intervention. PPARG, VEGFA, and TNF expression decreased and PPARA/CPT1A signaling pathway significantly increased after the intervention. Conclusion: Network pharmacology was used to predict the compounds and mechanism in Moringa oleifera against hyperlipidemia, which were confirmed by molecular docking and cellular assays, suggesting that Moringa oleifera leaves could be a potential therapeutic compound for reducing intracellular lipid levels.