High-altitude-associated skeletal muscle atrophy is a well-established phenomenon that is further responsible for the decline in physical performance. One of the major stressors of high altitude is hypobaric hypoxia, which contributes to disturbed redox homeostasis that further results in pathophysiological conditions, including skeletal muscle atrophy. Other recent research establishes the fact that hypobaric hypoxia-induced muscle protein loss is regulated via multiple pathways, including oxidative stress, inflammation, ER stress, disturbed calcium homeostasis, RyR1 remodeling, perturbed myokine profiling, altered anabolic pathways, enhanced protein degradation, and apoptosis in the skeletal muscle. Awareness of the molecular mechanism of altitude-linked muscle atrophy opens a way to develop strategies and interventions to ameliorate this protein loss. Nowadays dietary supplementation is gaining interest in amelioration of skeletal muscle atrophy and enhancing physical performance due to its safe profile, easy ingestion, and availability. Therefore, the present chapter sketches the details of the molecular mechanisms responsible for high-altitude-associated muscle protein loss and further sheds light on dietary intervention for managing the skeletal muscle health during stressful conditions.