This paper studies the effects of electromagnetic fields (EMF), specifically with circular electric field polarization, on the structure of Hemoglobin. Nearly all of the previous studies are based on linearly-polarized waves. But our comparative study based on a novel dual-polarized waveguide exposure device, shows that the EMF effects on macromolecules such as hemoglobin are polarization-dependent, and that circularly-polarized EMFs with the same incident power density can have significantly stronger effects on the structure of Hemoglobin. A novel dual-polarized exposure device is employed, followed by intrinsic fluorescence spectroscopy, UV–Vis spectroscopy, and far UV Circular Dichroism Spectroscopy, to show that the helical content is significantly reduced under circular as compared to linear polarization. This corresponds to a certain unwinding effect through the circularly-polarized EMF. The physical basis for the observed results is discussed together with implications for further research.