The rapid aging of the global population is leading to an increase in age-related conditions such as frailty, which significantly impacts health systems worldwide. Frailty is a multifaceted syndrome marked by diminished physiological reserves and a heightened vulnerability to stressors. Traditional interventions, including exercise and nutritional support, have yielded inconsistent results. This chapter explores the emerging role of mesenchymal stem cell (MSC) therapies in treating frailty by addressing the fundamental biological mechanisms of aging, such as cellular senescence, genomic instability, and inflammation. Preclinical studies have demonstrated MSCs’ potential to improve physical function, regenerate tissue, and modulate immune responses, offering new avenues for managing frailty. While early clinical trials have confirmed MSC therapy’s safety, its application in frailty treatment remains in development, with careful monitoring required to mitigate risks in elderly populations. Continued research is essential to optimize treatment protocols, assess durability, and standardize the use of MSCs for more effective frailty management.