Field effect transistor (FET) based biosensors that can translate directly specific bindings between receptors and target analytes to electrical signals have attracted considerable interests for label free, rapid, low-cost detection of biomolecules. However, it is challenging to detect biomarkers at low concentrations in physiological buffers with high ionic strengths due to the small Debye length. FET biosensors on a planar configuration are highly preferable because of the process compatibility with microelectronic manufacturing. III-nitride semiconductor materials have been considered as a promising candidate for biosensing applications due to their unique properties, such as chemical inertness, non-toxicity, and excellent thermal stability. In particular, III-nitrides FETs are ion-impermeable and highly stable in electrolytes, making them ideal for detection at ultralow concentrations in fluids with high ionic strengths. Here we present a recessed gate planar AlGaN/GaN heterojunction FET (HFET) for biodetection. The gate area of the AlGaN/GaN HFET was recessed by inductively coupled plasma (ICP) etching to shift the threshold voltage to near zero volt regime for sensitivity enhancement. As such, the device works at the subthreshold regime. The biosensing measurement was performed on a non-bias gate setting to eliminate the noise and electrochemical activities from the gate electrode. The signal-to-noise ratio of these recessed AlGaN/GaN FET biosensors is two orders of magnitude higher than that of the Si nanowire FET biosensors previously reported. Detection of streptavidin at concentration of 16 aM in PBS physiological buffer has been demonstrated. To the best of our knowledge, this is the highest sensitivity ever reported on a field effect-based biosensor in physiological buffer. These devices have demonstrated their potential in biochemical and clinical applications. We have successfully detected MIG (monokine induced by interferon gamma, an indicator of transplant rejection in patients when detected at a concentration level above nano Molar) in clinical samples. Utilizing of ion impermeable semiconductors like GaN opens up opportunities of FET-based biosensors for direct detection of biomarkers in physiological fluids at low concentrations for early disease diagnosis with excellent manufacturing compatibility.