〔Abstract〕 Objective To investigate the therapeutic mechanism of artemether in diabetic sarcopenia（DS）using network pharmacology and animal experiments. Methods Potential active components and therapeutic targets were screened using artemisinin as the parent compound. The predicted targets were intersected with DS-related targets, followed by construction of a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify the key biological processes and signaling pathways. Molecular docking was further used to evaluate the binding affinity between artemether and core targets. The DS mouse model was established using db/db mice, followed by artemether intervention. Fasting blood glucose, body weight, diabetes-related symptoms, body composition, grip strength, serum and skeletal muscle triglyceride levels, and muscle fiber cross-sectional area (CSA) were assessed. The expression levels of forkhead box O1 (FoxO1), Atrogin-1, muscle RING finger protein 1 (MuRF1), acyl-CoA synthetase short-chain family member 2 (ACSS2), carnitine palmitoyltransferase 2 (CPT2), and fatty acid-binding protein 3 (FABP3) in skeletal muscle were detected by qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry. In addition, metabolomics was performed to analyze changes in acylcarnitine metabolites in skeletal muscle. Results A total of 68 overlapping targets between artemether and diabetic sarcopenia (DS) were identified. The core targets included AKT1, FoxO1, NFKB1, FBXO32, and TRIM63, which were mainly enriched in the phosphoinositide 3-kinase/protein kinase B (PI3K-Akt) signaling pathway, forkhead box O (FoxO) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and insulin resistance-related pathways. Molecular docking analysis showed that artemether exhibited favorable binding affinity with the core targets. Animal experiments demonstrated that artemether reduced fasting blood glucose, ameliorated metabolic symptoms, increased lean mass and grip strength, decreased serum and skeletal muscle triglyceride levels, and increased muscle fiber cross-sectional area (CSA) in DS mice. In addition, artemether downregulated the mRNA and protein expression levels of FoxO1, FBXO32/Atrogin-1, TRIM63/MuRF1, ACSS2, CPT2, and FABP3, and improved the disturbance of acylcarnitine metabolism in skeletal muscle. Conclusion Artemether improves metabolic and skeletal muscle phenotypes in DS mice. Its effects may be associated with the amelioration of lipid metabolic disorders and the downregulation of FoxO1 and its downstream ubiquitin-proteasome pathway-related factors Atrogin-1 and MuRF1 in skeletal muscle.