Glutamate excitotoxicity is considered as the etiology of stroke and neurodegenerative diseases, namely, Parkinson's disease (PD), Alzheimer's disease (AD), and others. Meanwhile, substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc), a pivotal site in regulating orofacial nociceptive transmission via Aδ and C primary afferent fibers, majorly utilize glutamate as the principal excitatory neurotransmitter. Fucoxanthin (FCX), a carotenoid pigment extracted from brown seaweed, possesses various pharmaceutical properties including neuroprotective effect in multiple neuronal populations. To date, the direct activity of FCX on the SG of the Vc has not been extensively clarified. Consequently, we investigated the effect of FCX on excitatory signaling mediated by ionotropic glutamate receptors (iGluRs), using the patch-clamp technique recorded from SG neurons of the Vc. Here, FCX directly acted on glutamate receptors independent of voltage-gated sodium channel and γ-aminobutyric acid (GABA)