Homeostasis refers to the physiological processes by which an organism maintains its internal environment within a dynamic balance through negative feedback mechanisms. Disruption or failure of homeostatic mechanisms can lead to internal imbalances, potentially resulting in disease. Aging is closely associated with homeostasis, as the aging process often involves a decline in the body’s ability to regulate homeostasis, thereby increasing disease risk and leading to a decline in physiological function. SIRT2, a NAD⁺-dependent deacetylase belonging to the sirtuin family, plays a significant role in regulating cellular homeostasis and age-related diseases. This review discusses the multifaceted functions of SIRT2 in homeostatic medicine and aging interventions, along with its potential applications in disease treatment and anti-aging therapies.