Exposure to temperature variations can activate human physiological thermoregulation and increase energy expenditure. Moreover, regular exercising thermoregulation may improve glucose metabolism and even increases insulin sensitivity. Given that humans spend 80%-90% of their time indoors, indoor temperature variations may benefit our health. However, indoor temperature variations may cause thermal discomfort, which drives people’s behaviors to reduce the healthy thermal stimulus. To investigate possible solutions for bridging thermal comfort and metabolic health indoors, we evaluated a novel, personal thermal management system in moderately drifting temperatures (17-25˚C). This system allows personal free control but targets the most sensitive body parts (extremities in the cold and the head in the warm), leaving the rest of the body exposed to temperature dynamics. We conducted a controlled, randomized, cross-over study in an office-like climate chamber. Eighteen participants (nine males and nine females) completed two scenarios, one with the personal thermal management system and another without the system in 17-25˚C. Body thermoregulatory responses and thermal comfort were measured. The results reveal that the designed system did not affect whole-body thermoregulatory responses in most of the cases (skin temperature of unheated/uncooled body segments, skin blood flow of hands and feet, metabolism, subtract oxidation, physical activity). However, the thermal perceptions were significantly improved. Therefore, the personal thermal management system improves thermal comfort while keeping the physiological effectiveness of the temperature drift. These findings indicate that the targeted personal thermal management system is a promising solution for providing a comfortable and healthy office environment.