The Food and Drug Administration (FDA) has banned gamma-Hydroxybutyric acid (HBA), which is widely utilised for drug-facilitated sexual assaults across the world. As a result, it is crucial for law enforcement and drug organisations to detect HBA in biological settings. There has been substantial interest in 2D chemical nanosensors for gaseous and biological molecule detection. This paper studied the sensing performance of bare and Ir-decorated SiC nanosheets for HBA detection through the TPSS density functional. The bare SiC nanosheets were found to have insignificant responsiveness to HBA (almost 7.3 at 298 K) due to their small binding energy with the drug molecules (−0.26 eV). The Ir-decorated SiC nanosheets, however, showed superb performance in adsorbing HBA on an Si–C bond, with a binding energy of −2.54 eV. The Ir-decorated SiC nanosheets enabled strong HBA adsorption (binding energy = −1.35 eV). Therefore, the decoration of SiC sheets with Ir atoms remarkably enhanced their responsiveness to HBA molecules from 7.3 to 495.4. The recovery time for the desorption of HBA molecules from the surface of the Ir-decorated SiC nanosheets was estimated to be 1.09 s. It was concluded that Ir-decorated SiC nanosheets are a promising nanosensor to detect HBA.