Sarcopenia, characterized by age-related loss of skeletal muscle mass and strength, leads to serious health complications and increased societal costs. With its recent classification as an official disease in Korea, interest in developing therapeutic and functional food ingredients has grown. In this study, we screened 100 native Nicaraguan plant extracts to identify potential candidates for sarcopenia intervention. Using the MFDS-guided in vitro assay, mouse C2C12 myoblasts were differentiated into myotubes, pre-treated with extracts, and exposed to dexamethasone to induce muscle atrophy. Cytoprotective effects were evaluated by MTT assay. Anti-inflammatory activity was assessed by quantifying TNF-α and IL-6 secretion levels via ELISA. Several plant extracts exhibited significant protective and anti-inflammatory effects, indicating their potential as novel functional materials for muscle health. Among the 100 Nicaraguan native plant extracts evaluated, 15 extracts exhibited more than 20% cytoprotective activity against dexamethasone-induced muscle cell damage at concentrations of 100 μg/mL and 200 μg/mL. Of these, six extracts significantly reduced TNF-α and IL-6 secretion by more than 40% at 200 μg/mL. Notably, Crescentia alata Kunth (No. 36) showed superior cytoprotective and anti-inflammatory effects compared to the positive control, L-carnitine, without exhibiting cytotoxicity at the maximum concentration. To date, no scientific literature or patents have reported the muscle-protective or anti-inflammatory effects of this plant in muscle cells, suggesting its strong potential for development as a therapeutic agent or functional food for improving muscle function.