Obesity and its related metabolic disorders are highly prevalent in the elderly individuals. Low-grade chronic adipose tissue inflammation contributes to the onset and development of age-related insulin resistance and type 2 diabetes. There’s still lack of effective therapy for treatment of age-related metabolic disorders. The present study identified that α-mangostin (α-Man), a xanthone from Garcinia mangostana, remodels adipose tissue inflammation to mitigate age-related metabolic disorders. α-Man protected the mice against lipopolysaccharides (LPS)-induced acute adipose tissue inflammation, by reducing the expression of pro-inflammatory cytokines and chemokines and inhibiting the migration of macrophages into the adipose tissue and the pro-inflammatory polarization of macrophages. In a cohort of young (3-month) and old (18‒20 month) mice, α-Man mitigated age-associated adiposity, hyperlipidemia, and insulin resistance. α-Man alleviated age-related adipose tissue inflammation by reducing macrophage infiltration and pro-inflammatory polarization in visceral adipose tissue. Moreover, α-Man protected the old mice against liver injury through suppressing the secretion of microRNA-155-5p from macrophages. The above results demonstrate that α-Man, targeting adipose tissue inflammation, might represent a novel candidate to treat aging-related metabolic disorders and extend health-span.