Electric double layer was proved to modulate the channel of field-effect transistors, which is called electric-double-layer transistors (EDLTs) and have been reported previously. One of the unique property of the electric double layer is the much higher capacitance compared to that of silicon dioxide or other high dielectric constant materials. EDLTs are attractive not only because of its high capacitance, but also because of its other properties in solution, which is very different from conventional dielectric materials. In this study, we investigate the EDLTs using AlGaN/GaN HEMTs, with different designs of the devices and in solutions with different ionic strength. We find out that the channel conductivity is relevant to these parameters and the EDLT model becomes different from conventional FETs. By using the electric-double-layer AlGaN/GaN high electron mobility transistors, we successfully detect several proteins in physiological environment (1xPBS) with high ionic strength and in serum as well. Our devices and methods do not suffer from the charge screening effect, which is usually a critical issue for conventional FET-based biosensors. Direct detection of proteins in serum without any dilution or washing process can largely simplify the use of the FET-based biosensors for point-of-care or homecare. The results reveal future possible applications of the EDLTs.