This paper presents an analytical framework, based on the surface potential for a symmetrical double-gate AlGaN/GaN Metal oxide semiconductor high electron mobility transistor (DG-MOSHEMT) equipped with an embedded nanocavity tailored for biomedical sensing applications. The proposed model operates on the dielectric modulation principle and meticulously scrutinizes the device’s performance using critical sensing metrics such as threshold voltage shift (ΔVth), threshold voltage sensitivity (SVth), surface potential shift (ΔΨs,0), and surface potential sensitivity (SΨs,0). The model demonstrates remarkable sensitivity in detecting minute biomolecule variations, explicitly focusing on streptavidin, uricase, protein, and ChOx as the target biomolecules. Additionally, analytical equations based on surface potential are established to accurately determine gate charges (QG), gate-to-drain capacitance (CGD), and gate-to-source capacitance (CGS). The thorough investigation of biomolecule effects on gate capacitance holds paramount significance as it plays a vital and profound role in dictating device performance. Furthermore, variations in nanocavity length, AlGaN layer thickness, and oxide layer thickness are explored to understand their influence on ΔVth and SVth. The proposed model exhibits a remarkable improvement in both threshold voltage shift and sensitivity compared to the single MOS-HEMT. Notably, it demonstrates substantial enhancements of 2.06, 1.72, 1.49, and 1.5 times for the uricase, streptavidin, protein, and ChOx biomolecules, in terms of threshold voltage shift, and impressive improvements of 10.7%, 14.5%, 18.2%, and 50% for the same biomolecules, respectively, in terms of threshold voltage sensitivity, surpassing the previous findings. Uricase exhibited the most significant shift in surface potential (ΔΨs,0) among the analyzed biomolecules, with a value of 100 mV mm−1 and a sensitivity (SΨs,0) of 0.44. In contrast, ChOx showed a modest (ΔΨs,0) of 24 mV mm−1 with a relative sensitivity (SΨs,0) value of 0.108. Increasing nanocavity length and oxide layer thickness positively contribute to ΔVth and SVth. Moreover, while an increase in AlGaN layer thickness enhances ΔVth performance, its impact on SVth is minimal.