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The hypothalamus in the central nervous system (CNS) has important functions in controlling systemic metabolism. A calorie-rich diet triggers CNS immune activation, impairing metabolic control and promoting obesity and Type 2 Diabetes (T2D), but the mechanisms driving hypothalamic immune activation remain unclear. Here we identify regulatory T cells (Tregs) as key modulators of hypothalamic immune responses. In mice, calorie-rich environments activate hypothalamic CD4 + T cells, infiltrating macrophages and microglia while reducing hypothalamic Tregs. mRNA profiling of hypothalamic CD4 + T cells reveals a Th1-like activation state, with increased Tbx21 , Cxcr3 and Cd226 but decreased Ccr7 and S1pr1 . Importantly, results from Treg loss-of function and gain-of-function experiments show that Tregs limit hypothalamic immune activation and reverse metabolic impairments induced by hyper-caloric feeding. Our findings thus help refine the current model of Treg-centered immune-metabolic crosstalk in the brain and may contribute to the development of precision immune modulation for obesity and diabetes. Hypothalamus participates in systemic metabolic processes, while high calorie intake increases immune activation in the central nervous system. Here the authors show that reduced regulatory T cells in the hypothalamus contribute to elevated immune activation in a high calorie environment, thereby prompting a potential therapy target for metabolic diseases.