Sarcopenia, characterized by the degeneration of skeletal muscle tissue, has emerged as a significant concern in recent years. This increased awareness stems from advances in research focusing on elderly patients, which have revealed correlations between aging mechanisms and muscle degeneration, beyond the mere fact that tissues age and deteriorate over time. Consequently, the present study aims to address sarcopenia by developing and evaluating DPPC lipid vesicles that encapsulate three distinct drugs: HMB, NMN, and L-Leucine. These drugs are specifically selected for their properties, which facilitate effective interaction with the affected muscle tissue, thereby promoting desired therapeutic effects. Preliminary physicochemical analyses indicate the successful formation of spherical lipid vesicles, characterized by nanometric dimensions and stable membrane integrity. The biological investigations aimed to highlight the potential of DPPC lipid vesicles encapsulating HMB, NMN, and L-Leucine to alleviate sarcopenia-induced cytotoxicity and oxidative stress. Through a comparative evaluation of the three drug formulations, we demonstrate that drug-loaded DPPC vesicles effectively mitigate oxidative damage, preserve mitochondrial function, and maintain cytoskeletal integrity in HO-induced C2C12 myotubes, with HMB-loaded vesicles showing the strongest protective effects against muscle degeneration. These findings underscore the therapeutic potential of DPPC-based controlled release systems for sarcopenia treatment and highlight the need for further investigations into their mechanistic role in muscle preservation.