The commencement of the presented project was by screening of natural compounds extracted from neuroactive endogenous medicinal plants. Explicitly, ferutinin (Ferula hermonis L.), thymoquinone (Nigella sativa L.), eugenol (Syzygium aromaticum L.) and 6-gingerol (Zingiber officinale L.) were tested for their protective effect against neurodegeneration utilizing Glycine receptors (GlyRs) in vivo model. None of these compounds were reported before to modulate the in vivo GlyRs. GlyRs are inhibitory key mediators of synaptic signaling in spinal cord, brain stem, and higher central nervous system regions. Neurodegeneration may cause alteration of the GlyRs causing strychnine-like convulsions and stiffness. Modulation of GlyRs in vivo was studied in a mouse model of strychnine toxicity. Ferutinin revealed to be potent modulators to GlyR; with potential anticonvulsant properties in low doses. Thymoquinone, eugenol and 6-gingerol when given together with strychnine, in low concentrations reduce strychnine toxicity by reversing strychnine toxicity in mice. It could be concluded that all compounds under investigation could be used as sedatives in low doses. In order to fight against neurodegenerative diseases is to improve body antioxidant, the compounds under investigation provided to be good sources for antioxidant potential. In brief, ferutinin, thymoquinone, eugenol and 6-gingerol suggested being novel GlyR modulators, good phytochemicals, pharmacological tool and a dose sensitive drug to treat stiffness, convulsions and prophylactic agents to guard against neurodegenerative disorders.