Neonatal glycine encephalopathy is a rare genetic neurometabolic disorder secondary to glycine cleavage system deficiency. Patients typically present with early-onset intractable seizures, status epilepticus and encephalopathy. Seizures control remains challenging in view of their refractoriness to standard anti-seizure medications. Sodium benzoate is commonly used to control the elevated glycine level. Oral anti-NMDA receptor antagonists, ketamine and dextromethorphan, have been used in various combinations in the treatment of this complex disorder. In this report, we present a neonatal case of classical glycine encephalopathy with hypotonia and refractory myoclonic seizures. The status epilepticus was successfully treated using a combination of intravenous ketamine, oral dextromethorphan and sodium benzoate. Seizures resolved and the patient's development showed improvement on follow-up. The intravenous form of ketamine in the neonatal period is rarely used, and it has been reported in only two glycine encephalopathy patients in the literature. This is the first report in the literature of the efficacy of intravenous ketamine using the above triple therapy. This intervention might have implications on the management of neonatal intractable seizures in glycine encephalopathy, which might improve the outcome of this devastating disorder.