Sarcopenia, defined as the progressive decline of muscle mass, strength, and function, severely compromises autonomy and quality of life in older adults. This systematic review evaluated synergistic effects of protein supplementation combined with resistance exercise on biochemical and functional biomarkers of sarcopenia. The search for scientific evidence was conducted in PubMed, Scopus, ScienceDirect, and Cochrane databases (2019–2025), applying explicit inclusion and exclusion criteria, like only randomized controlled trials in humans, published in English, Spanish, or French, were included to ensure high-quality evidence. After selection, the risk of bias of the articles was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Seven randomized controlled trials, with a total of 260 participants, met the eligibility criteria. Interventions combining resistance exercise three times per week at 60–80% of one-repetition maximum with daily protein supplementation of at least 15 g, mainly from dairy sources, showed synergistic effects. Improvements were observed in inflammatory and anabolic biomarkers, with reductions in myostatin, activin, and IL-6, and increases in IGF-1, follistatin, and IL-10. Functional outcomes included gains in muscle strength, fat-free mass, and muscle fiber cross-sectional area. Despite heterogeneity in duration and sample size, findings support this combined approach as a promising and clinically applicable strategy to prevent and treat sarcopenia. No external funding was received, and the review is registered in PROSPERO (CRD42025640989).
