Objective: To analyze the effective ingredients and molecular mechanisms of Shenling Baizhu powder (SLBZP) in the treatment of metabolic associated fatty liver disease (MAFLD) through network pharmacology technology and experimental validation. Methods: The active components and targets of SLBZP were obtained from the TCMS databases, and the GeneCards, TTD and DisGeNET databases were used to predict and screen for MAFLD-related genes. An "herb-active components-crossover targets" network was constructed using Cytoscape3.7.2 software. STRING11.5 was applied to the construction of the PPI network. GO and KEGG analysis were performed to investigate the biological processes and pathways involved in SLBZP. Molecular docking was performed using AutoDock Vina1.1.2 to validate the binding ability between active compounds and core crossover targets. Subsequently, the potential mechanism of SLBZP on MAFLD predicted by network pharmacological analysis was experimentally studied and verified. Results: 122 active components participated in the 41 MAFLD-related targets identified in SLBZP. The PPI network revealed that ALB, TNF, IL1B, PPARα, PPARγ, HMOX1, PTGS2, IL6 and ADIPOQ were the core crossover targets. The number of common targets between the SLBZP and MAFLD was 263 GO biological process items and 42 KEGG signal pathways were obtained after analysis. The main compounds and the target protein had a good binding ability in molecular docking. Through experimental results, SLBZP was shown to be effective in ameliorating lipid accumulation and hepatic steatosis in high-fat diet-fed rats and PA-induced HepG2 cells to prevent MAFLD. And the results of cellular experiments suggest that SLBZP may improve MAFLD through the AMPK signaling pathway. Conclusion: SLBZP effectively ameliorates lipid accumulation and hepatic steatosis in MAFLD, and the mechanism may be related to the AMPK signaling pathway.