Muscular strength and endurance are vital for physical fitness. While mistletoe extract has shown efficacy in significantly increasing muscle strength and endurance, its accessibility is limited. This study explores combining mistletoe and apple peel extracts as an effective muscle health supplement. Analyses of histology, RNA, and protein in the combined extract-treated mouse group demonstrated significant enhancements in muscle strength and endurance, evidenced by larger muscle fibers, improved mitochondrial function, and a higher ratio of type I and IIa muscle fibers. Combining half doses of each extract resulted in greater improvements than using each extract separately, indicating a synergistic effect. Pathway analysis suggests that the observed synergy arises from complementary mechanisms, with a mistletoe extract-induced decrease in myostatin (MSTN) and an apple peel extract-induced increase in IGF1, leading to a sharp rise in AKT, S6K, and MuRF1, which promote myogenesis, along with a significant increase in PGC-1α, TFAM, and MEF2C, which are critical for mitochondrial biogenesis. This research provides practical insights into developing cost-effective, natural supplements to enhance muscle performance and endurance, with potential applications in athletic performance, improving muscle growth and endurance in children, and addressing age-related muscle decline.