Background: Muscle atrophy means a progressive decrease in muscle mass, strength, and quality and has a lot of discomfort in daily life. High-dose or continuous use of glucocorticoids (GCs), which are negative muscle regulators, led to the risk of muscle atrophy and weakness. Up to now, the effect and the underlying mechanism of Citri unshius Pericarpium (CP) on muscle atrophy have not been fully elucidated. Objectives: Accordingly, the current study was performed to evaluate the effects and the underlying mechanisms of CP on dexamethasone (DEX)-provoked muscle atrophy in C57BL/6 mice. Materials and Methods: The 8-week-old mice were treated once a day (DEX 20 mg/kg body weight, i.p.), and CP was administrated orally for 10 days. Then, we measured the body weight, swimming time, and muscle weight, and histological evaluation and western blot were performed. Results: CP improved muscle function decline by bettering the swimming time and muscle weight to some extent. Moreover, histological muscle damage induced by DEX was enhanced through CP treatment. CP treatment induced the reduction of ROS-related factors. CP showed a decrease in the protein expressions such as myostatin, Atrogin-1, and MuRF1 via the down-regulation of the phosphorylation of AMPK. Besides, in the CP group, muscle protein synthesis was increased by the PI3K/Akt/mTOR signaling pathway. Conclusion: Taken together, CP could be highly commercialized as a commercial material for functional food for the prevention and improvement of muscle loss, which is induced by muscle atrophy.