Long-acting local anaesthetics have demonstrated effectiveness in managing intraoperative and postoperative pain. However, substances like lidocaine and paraben preservatives can trigger allergic reactions and methemoglobinemia in susceptible individuals. While bupivacaine shares common side effects with other local anesthetics, its adverse effects are amplified due to the physicochemical properties of long-acting local anesthetics. Recently, there has been growing interest in utilizing saliva as a potential bio matrix for drug testing because the drug concentration in saliva directly reflects the free, non-protein-bound drug in plasma. This study involved extracting lidocaine and bupivacaine from saliva collected from healthy male patients using a liquid-liquid extraction method. Gas Chromatography-Mass Spectrometry (GC-MS) with ropivacaine as an internal standard was employed for simultaneous determination of both drugs. The results demonstrated high precision and accuracy, with a limit of detection (LOD) and limit of quantification (LOQ) of 3 ng/ml and 10 ng/ml for lidocaine, and 20 ng/ml and 62 ng/ml for bupivacaine, respectively. This non-invasive and user-friendly method provides highly accurate drug analysis results.