In this paper, we focus on recent advances of the high-electron-mobility transistor (HEMT)-based biosensors for the detection of various biomolecules. The vital utilization of biosensors in various domains leads to standard, accurate and powerful biosensors as it possesses a huge potential to attain information in a faster and simple manner in comparison to conventional assays. Amongst various biosensors, high electron mobility transistors (HEMTs) proved more potential and immense advantages due to their inherent material properties such as higher electron mobility, two-dimensional electron gas (2DEG), chemically inert, stable at high temperature and high speed. This review paper features the basic related concepts of HEMT based biosensors in terms of structure-oriented, different methodologies, the significance of various biomarker and biomolecules. This review also describes the crucial factors which influence the various performance matrices of a biosensor such as sensitivity, selectivity, specificity, reliability, repeatability, and stability. A comparison of different HEMT based biosensors with Si-based biosensor is also analyzed. This review will help researchers to get all the information regarding HEMT based biosensors at one place to work further for developing next-generation biosensors.