Objective To analyze the role of dandelion and mulberry leaf in the progression of acute myeloid leukemia （AML） by network pharmacology， and to clarify the active components and their mechanisms in treating AML. Methods The active components of dandelion and mulberry leaf were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The targets were predicted by SwissTargetPrediction Database. The AML-related genes and protein targets were retrieved from the SymMap Database， the GeneCards Human Gene Database， the DisGeNET Database， and the Online Mendelian Inheritance in Man （OMIM） Database. The AML-related genes and target genes of dandelion and mulberry leaf were compared by comparative analysis and were identify by the enrichment genes， followed by Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis. The drug-active component-target network and protein-protein interaction （PPI） network were constructed by Cytoscape 3.8.0 software， and the core genes were selected by CytoNCA plugin； the molecular docking was conducted by AutoDock software. Results After filtering by databases， 39 active components were identified， and 148 common targets between dandelion-mulberry leaf and AML were collected. The GO functional enrichment analysis mainly involved cytokine-mediated signaling pathways， positive regulation of kinase activity， and oxidative stress responses. The KEGG signaling pathway enrichment analysis focused on the phosphatidylinositol 3 kinase/protein kinase B （PI3K-AKT） signaling pathway， the tumor necrosis factor （TNF） signaling pathway， and the Janus kinase/signal transducer and activator of transcription （JAK-STAT） signaling pathway. The key targets were identified by topological analysis including signal transducer and activator of transcription 3 （STAT3）， epidermal growth factor receptor （EGFR）， protein kinase B1 （AKT1）， recombinant human epidermal growth factor （EGF）， vascular endothelial growth factor A （VEGFA）， oncogene MYC， tumor protein P53 （TP53）， mitogen-activated protein kinase 3 （MAPK3）， cysteiny asparate specific protease-3 （CASP3）， oncogene SRC， heat shock protein 90 alpha family class A member 1 （HSP90AA1）， tenascin XB1 （CTNNB1）， phosphoinositide kinase-3 catalytic subunit alpha （PIK3CA）， interleukin 6 （IL-6）， TNF， mitogen-activated protein kinase 1（MAPK1）， and phosphatidylinositide kinase-3 regulatory subunit 1 （PIK3R1）. The molecular docking results showed the highest affinity pairing to be taraxerol with MYC （-8.74 kcal·mol^-1）， and quercetin， kaempferol， luteolin， and artemetin demonstrated good binding affinities with various targets. Conclusion The main active components of dandelion-mulberry leaf， such as quercetin， taraxerol， kaempferol， luteolin， and artemetin， may exert the anti-AML effect by regulating AKT1， STAT3， HSP90AA1， IL-6， and MAPK1； regulation the PI3K-AKT signaling pathway may be the critical mechanism of anti-AML effect by dandelion-mulberry leaf.