In addition, neuroinflammation is evidenced by neuroglial cell activation and pro-inflammatory cytokine release, which was suggested to enhance epileptic seizures Glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-\(\alpha\)), and nuclear factor kappa B (NF-\(\kappa\)B) were some of the reported cytokines that induce neuronal hyperexcitability and result in seizures development [10,11]. To date, there are many available antiepileptic drugs (AEDs) such as valpro acid, phenytoin, phenobarbital, and newer drugs, including topiramate, tiagabine, and oxcarbazepine. AEDs can treat epileptic seizures through different mechanisms, including sodium and calcium channel blockers, gamma-aminobutyric acid (BABA) enhancers, glutamate blockers, and neurotransmitter modulators, resulting in different efficacies and side effects [12]. Most AEDs are associated with side effects such as liver damage, teratogenicity, gastrointestinal disturbances, drowsiness, fatigue, depression, sleep disorders, and continued or recurrent seizures [13]. Since the treatment goal is having no seizures with no adverse effects, finding an efficient novel antiepileptic drug with no side effects is essential. Incorporating nanomaterials in the biological and medical fields is a good way to obtain the highest efficiency and safety; metal-based nano therapies have been used to treat neurodegenerative diseases such as Alzheimer's disease [14]. The cellular responses to nanoparticles and their uptake are directly affected by their size, shape, coating, agglomeration, and dissolution rate [15]. Selenium (Se) possesses an antioxidant activity with a main role in the immune response and thyroid gland function [16]. Selenium nanoparticles (SeNPs) have been involved in the therapeutic field because of their bioactivity and low toxicity; they have been applied as an antioxidant, antifungal, antimicrobial, and anti-cancer [15,17]. In addition, SeNPs showed antioxidative, anti-inflammatory, anti-apoptosis, and neuro-modulatory effects, as concluded in previous in vivo studies of epilepsy treatment [3,18]. Biogenic SeNPs were more biocompatible and stable than the chemical-based SeNPs, which enabled their applications in the medical field [19,20]. Many researchers have already synthesized SeNPs using extracts of different plants, such as Hawthorn (berries), Allium (garlic), and Berberis vulgaris (barberry) successfully [15,21,22]. Plant-based SeNPs were reported to treat hepatic, renal, and neuronal toxicities [18,19]. _Syzygium aromaticum_ (clove) is one of the widely used medicinal plants in treating many disorders; this is owing to its therapeutic roles, including antimicrobial, anti-cancer, and antioxidant effects [23,24]. _Syzygium aromaticum_ extract (SAE) possesses these therapeutic properties because of the presence of eugenol, carvacrol, thymol, and cinnamaldehyde [25]. To date, the antiepileptic effect of SAE either delivered alone or with SeNPs has not been investigated yet. Furthermore, we recently confirmed the antiepileptic effect of SeNPs biosynthesized with prodigiosin, a red dye naturally produced by various bacterial species [26]. Thus, the current study aimed to find the potential antiepileptic effect of green synthetized SeNPs using SAE against the epileptic seizures and cortical damage induced by pentylenetetrazo (PTZ) injection in rats and its mechanism.