The global population is undergoing rapid aging, making physical activity a crucial element in preventing mortality and lowering the risk of Alzheimer's disease. Age-related declines in muscle mass and cognitive abilities significantly contribute to frailty and dependency. Thus, this study focuses on a meticulous analysis of the protective effects of multidomain interventions, an emerging resource combating age-related declines. It seeks to underscore their profound impact on cognitive flexibility and sarcopenia, highlighting their pivotal role in mitigating the adverse effects of aging. To identify relevant randomized controlled trials up to November 2023, we reviewed eight online academic databases, following PERSiST guidelines, PRISMA reporting system, and PICOs criteria. Meta-analyses on selected functional outcomes utilized a random-effects model, including the Timed Up and Go Test, Sit to Stand Test, Victoria Stroop Test, and Trail Making Test. Out of 2082 scrutinized articles, 17 were included in the systematic review, and 8 in the meta-analysis. Positive effects (p = 0.05, I(2) = 57%; 95% CI - 0.63 to - 0.05) were observed in cognitive flexibility for certain interventions. Similarly, interventions addressing muscle strength demonstrated improvements in the Sit to Stand Test for the exercise group compared to the control group (p = 0.02, I(2) = 0%; 95% CI - 0.63 to - 0.05). These findings underscore the importance of incorporating physical activity as a primary component of public health interventions for promoting healthy aging and reducing the burden of age-related diseases. Future interventions may explore more homogeneous approaches and evaluate the impact of thrice multidomain weekly sessions.