Hydrogen sulfide (H₂S) is increasingly recognized as gaseous endogenous molecule for its significant role in various physiological processes, behind its historical association with toxicity. Recent studies have highlighted H₂S’s cytoprotective properties, including antioxidant, anti-inflammatory, and antifibrotic effects, particularly in the context of skeletal muscle (SKM) health. SKM disorders, such as muscular dystrophy, human malignant hyperthermia, and sarcopenia, lead to severe structural and functional impairments that adversely affect the quality of life. Although limited literature is available on the role of H2S in SKM physiopathology, it is gaining special interest. Emerging evidence suggests that H₂S may have a protective role in mitigating muscle damage and dysfunction. This chapter explores the dual functions of H₂S in SKM physiology and pathophysiology, emphasizing its potential therapeutic applications. We propose that H₂S-based strategies may offer promising avenues for alleviating the progression of muscle-related disorders and warrant further investigation to fully elucidate its mechanisms of action.