Blood heat exchangers (BHEs) are critical for extracorporeal therapies, yet conventional designs typically exhibit suboptimal cooling efficiency along with elevated risks of coagulation and hemolysis. The present work introduces a thermoelectric cooling-based helical multistage blood heat exchanger (THM-BHE) to achieve rapid and precise temperature control. The helical flow channel design and multistage cooling strategy enhance temperature uniformity of blood while minimizing coagulation and hemolysis risks. Through numerical simulation, the structure of THM-BHE was optimized, and its performance was comprehensively evaluated. in vitro experiments verified the precise thermoregulatory capability of the heat exchanger during brain cooling, and transient thermal analysis further indicated a rapid temperature response. in vivo validation employing a porcine model confirmed the clinical reliability of the THM-BHE, successfully reducing tympanic temperature from 34.3 degrees C to 30.1 degrees C within 60 min. Comparative studies showed that gradient cooling strategy offered superior safety profiles, highlighting THM-BHE's potential in precise blood temperature regulation for brain cooling.