Introduction This database includes the raw data linked with the paper “ Therapeutic Salivary Monitoring of Perampanel in Patients with Epilepsy Using a Volumetric Absorptive Microsampling Technique” published in “pharmaceutics”. The present work describes the development and validation of a volumetric absorptive microsampling (VAMS) method combined with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the quantitative determination of the antiseizure medication perampanel in oral fluid and its clinical applicability in patients with epilepsy. VAMS tips were loaded with 30 μL of oral fluid, dried for 60 minutes and placed into clean tubes. Analytes were extracted with methanol and the samples were incubated at 50°C, sonicated and centrifuged. The supernatant was evaporated at room temperature under a gentle stream of nitrogen and reconstituted with 60 μL of methanol. Separation and quantification were achieved on a monolithic column connected to a mass spectrometer. Calibration curves were linear between 0.5 and 300 ng/mL. Intra- and inter-day accuracy was within 85.6-103.2% and intra-day and inter-day precision did not exceed 12.1%. Mean extraction recoveries ranged from 81.3% to 98.7%. Perampanel was stable in samples collected by VAMS and stored under different storage conditions. The developed VAMS-LC-MS/MS method was validated according to internationally accepted criteria and showed adequate bioanalytical performances holding great potential as alternative strategy to support domiciliary TDM in patients with epilepsy treated with perampanel according to the simplicity of samples collection.