The loss of lean body mass, muscle strength and physical function causes significant problems in older adults. Protein and amino acid supplements can preserve muscle strength but the effect on function is variable. We conducted a systematic literature review and meta-analysis to investigate the effect of protein and amino acid supplementation on fat-free mass, muscle strength and physical function in malnourished, frail, sarcopenic, dependent or elderly with acute or chronic conditions, with or without rehabilitation exercise. Databases searched included Medline, BIOSIS, CINAHL, Cochrane Library, EBM Reviews, Embase, Pre-Medline, ProQuest, PubMed and Scopus. Retrieved articles were assessed by two reviewers using the Cochrane Risk of Bias (ROB) Tool. In all, thirty nine randomised controlled trails (n 4274) were included. The studies used a range of protein or essential amino acid (EAA) supplements in a variety of settings, including hospital, community and long-term care. Only seven studies had low ROB and no effect of supplementation was found on any outcomes. Analysis of all thirty-nine studies suggest protein and EAA supplements may improve fat-free mass, muscle strength and physical function (standardised mean difference 0·21–0·27, all P<0·005), but significant heterogeneity and ROB was evident. Predetermined subgroup analysis found undernourished elderly benefitted most; EAA were the most effective supplements and small beneficial effects were seen without rehabilitation exercise. The high heterogeneity and few studies with low ROB limits the conclusions and more high quality studies are needed to determine the best nutritional strategies for the maintenance of strength and function with increasing age.