Type 2 diabetes mellitus (T2D) patients often display drastic hyperarousal-related clinical anomalies such as fear, panic, nervousness, pain, and seizures. Consequently, hyperarousal patients with inadequate metabolic outcomes (hyperglycemic condition) are usually treated with drugs targeting blockade of sodium/calcium channels, augmentation of the inhibitory (GABA) neurotransmission, and reduction of excitatory (glutamatergic) neurotransmission to achieve a “hypoarousal” state. This perilous clinical-pathological condition of hyperglycemia and hypoarousal may result in severe learning disability and cognitive impairment. Unfortunately, there is little evidence suggesting the synergistic effect of hypoarousal and hyperglycemia on cognition. Hence, this study was designed to evaluate the in vivo effect of Alloxan (pyrimidone, barbituric acid derivative) and Phenytoin (hydantoin-barbiturate) on rodent cognition. Furthermore, we also performed in-silico studies on these compounds on GABA-A & Insulin receptors, Sodium Channels, and GLUT-4 transporter. Administration of Alloxan and Phenytoin evoked severe learning and cognitive deficiency using behavioral studies (elevated plus maze, Y-maze, Hebb’s William maze, and passive avoidance test). Our results indicated that this might serve as a valid animal model to identify new/novel therapeutic medications for hyperglycemic and hypoarousal- related learning and cognitive deficiency.