Radiant cooling (RC) systems are increasingly implemented in public buildings to enhance human thermal comfort and reduce building energy consumption. The quality of the indoor thermal environment significantly impacts occupants’ learning and work performance. This investigation explores indoor occupants’ dynamic physiological regulation, thermal comfort, and cognitive performance under radiant whole-wall cooling (RWWC) systems. Twenty-eight participants underwent a summer exposure test task at varying ambient temperatures, yielding four collected data types: indoor physical parameters, physiological parameters (including skin temperature (ST), heart rate (HR)/heart rate variability (HRV), and electroencephalography (EEG)), performance index (PI), and thermal perception. Results indicate that the RWWC system notably improves thermal perception and comfort, with 93 % of participants reporting comfort at a target temperature of 24℃. Air temperature (AT) exerted the most significant effect on changes in ST on the right upper arm (p < 0.01) and left hand back (p < 0.01) at 30℃ compared to the 22℃. The difference in whole-body mean skin temperature (MST) is 2.68℃. The HR decline was more pronounced in higher temperatures, and the HRV representativeness index approached ‘1′ at 24℃. PI was affected by temperature and task type, displaying a non-linear correlation with AT (R2 = 0.6056) and an inverted “U” shaped curve with TSV (R2 = 0.9523). Thermal perception correlates with MST, HRV, and EEG. The study carries implications for the reasonable design of comfortable and healthy RC environments.