Skeletal muscle is an organ that regulates biological metabolic energy. Its dysfunction causes decline of body functions and disability, thus deteriorating the overall quality of life. Various materials are being developed with an anti-sarcolytic effect. However, anti-sarcolytic effect of Sinomenium acutum rhizomes extract (SAE) remains unclear. Therefore, this study aimed to investigate anti-muscle atrophy effects of SAE and its alkaloids, including sinomenine (SIN), magnoflorine (MF), acutumine (ACU), and N-ferultyramine (NFT) isolated from SAE, on dexamethasone (Dex)-induced myotubules. C2C12 myogenic cells differentiated for 6 days were treated with 1 mM Dex for 24 hours. Induction of muscular atrophy was confirmed by a decrease in myogenin expression. We found that Dex increased expression levels of muscle-specific ubiquitin ligases MuRF1 and MAFbx/atrogin-1. However, mRNA and protein levels of these muscle-specific ubiquitin ligases were significantly reduced by cotreatment with SIN, MF, and NFT in myotubes. Glucose uptake reduced by Dex in myotubules were also restored by SIN, MF, and NFT treatments. These results suggest that SIN, MF, and NFT can reduce muscle wasting and enhance glucose uptake in Dex-treated myotubes, highlighting their potential as therapeutic agents to prevent muscle atrophy.