Aging is an inexorable pathophysiological progression characterized by the overwhelming deterioration of tissue integrity and cellular function coupled with increased risks of various aging-related diseases. Demographic shifts toward extended longevity have precipitated a paradigm shift in disease epidemiology, in which neurodegenerative conditions and cardiovascular pathologies now constitute predominant determinants of morbidity and mortality in geriatric populations. These conditions severely erode functional autonomy in aging populations and strain healthcare infrastructures globally. As a principal nicotine adenine dinucleotide-dependent deacetylase within mitochondria, sirtuin 3 (SIRT3) exerts multimodal regulatory effects spanning mitochondrial bioenergetics, oxidative stress, and epigenetic modifications associated with aging. This review summarizes recent discoveries regarding the involvement of SIRT3 in physiological aging and its pathophysiological intersections with major aging-related disorders, providing new insights and ample inspiration for future research aimed at slowing the aging process and improving outcomes in aging-related diseases.