Natural killer cells (NKs) are lymphocytes of the innate immune system that quickly respond to viruses, infections, and tumors during their short cell life cycle. However, it was recently found that NKs undergo quantitative, distributional, structural, and functional phenotypic changes during aging that suppress immune responses, which is known as immunosenescence. The aging host environment, cytokine regulation, cytomegalovirus status, and hypothalamic‒pituitary‒adrenal axis have significant effects on NK function. Different lifestyle management interventions modulate the number and cytotoxic activity of NKs, which are essential for rebuilding the immune barrier against pathogens in elderly individuals. Based on recent studies, we review the phenotypic changes of and potential threats of NKs during aging and explore the underlying mechanisms. By summarizing the effects of lifestyle management on NKs and their application prospects, we aim to provide evidence for enhancing immune system function against immune diseases in elderly individuals.