We investigate the performance of a dielectric modulated dual-metal double-gate with low-k/high-k oxide stack junctionless MOSFET (DM-DG-LK/HK-S JL-MOSFET) based sensor device for successful detection of different protein molecules in dry environment condition, in terms of the absolute and relative change in the threshold voltage (Vth), called Vth-responsivity and Vth-sensitivity, respectively. The influence of work-function difference of the DM-gate along with the position of cavity containing biomolecules, followed by the impact of cavity dimension, on the sensing metrics, have been thoroughly inspected. Furthermore, the optimization of cavity dimension, along with proper DM-gate work-function engineering is done for the wide range of protein detection. For the sensor device, having channel length (Lch) of 1 μm, this optimum cavity dimension is found to be (400 nm × 10 nm). It is observed that, the device with Lch = 1 μm exhibits superior sensing performance when, along with the source-side cavity, the drain-side gate metal has got higher work-function than the source-side gate metal (i.e., ɸM2 > ɸM1), compared to the case when ɸM1 > ɸM2 and the cavity is located near the drain-side. Respective performance enhancements, in terms of percentage improvement of Vth-responsivity and Vth-sensitivity, are found to be 250% and 263% for the detection of Staphylococcal nuclease. Similar trend is found for the sensor devices with Lch = 50 nm. © 2020, Springer Nature B.V.