Nanofabricated gold nanoparticles (Au-NPs) on MoS₂ nanosheets (Au-NPs/MoS₂) in back-gated field-effect transistor (BG-FET) are presented, which acts as an efficient semiconductor device for detecting a low concentration of C-reactive protein (C-RP). The decorated nanomaterials lead to an enhanced electron conduction layer on a 100-μm-sized transducing channel. The sensing surface was characterized by Raman spectroscopy, ultraviolet–visible spectroscopy (UV-Vis), atomic force microscopy (AFM), scanning electron microscopy (SEM), and high-power microscopy (HPM). The BG-FET device exhibits an excellent limit of detection of 8.38 fg/mL and a sensitivity of 176 nA/g·mL⁻¹. The current study with Au-NPs/MoS₂ BG-FET displays a new potential biosensing technology; especially for integration into complementary metal oxide (CMOS) technology for hand-held future device application.