The effective management of epilepsy requires analytical tools capable of addressing the lack of specific biomarkers, and current antiepileptic drugs (AEDs) suffer from response variability, a narrow therapeutic index, and unpredictable neurotoxicity. Traditional approaches to quantitative drug monitoring not only fail to deliver precise, real-time results necessary to personalized treatment options, but also to prevent AED-induced neurotoxicity Emerging sensing platforms that combine innovative nanotechnology approaches and engineered microfabricated transducers provide sensitive and selective quantification of main AEDs that include sodium, potassium, and calcium channel modulators, γ-aminobutyric acid (GABA) drugs, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists, and synaptic vesicle protein 2A (SV2A) ligands. In this review, we present a comprehensive mechanism-based overview of sensors engineered for AEDs monitoring, covering design methods and assay techniques. The presented approaches utilized cutting-edge materials, including graphene and 3D carbon structures, gold nanoparticles, quantum dots, and metal-organic frameworks (MOFs), to achieve sensitive and selective detection in various bodily fluids, such as brain interstitial fluid, blood, sweat, urine, saliva, and exhaled breath condensate. Exploring key areas of AEDs sensing could not only advance understanding and monitoring of therapeutic responses and provide comprehensive insights into brain injury, but also offer a new perspective on AEDs management. Incorporating these sensing platforms into AEDs management systems could facilitate real-time dose adjustments and efficacy monitoring, ultimately improving seizure risk assessment.