Toxic leukoencephalopathy is a disorder characterized by the alteration of myelin in white matter tracts secondary to exposure to neurotoxic substances. Here we describe a case of a middle-aged woman who presented to the emergency department with a history of bizarre behaviour, speech abnormalities and generalised muscle stiffness caused due to recent opioid overdose. Further investigations and extensive neurological tests, including magnetic resonance imaging (MRI) scan of the brain, demonstrated features consistent with toxic leukoencephalopathy (TLE). The patient was managed conservatively with the care of a multidisciplinary team involving a dietician, physiotherapist and speech and language therapist. She showed gradual and slow but significant recovery following a period of neurorehabilitation. The clinical presentation of TLE varies but MRI typically shows diffuse bi-lateral white matter lesions. History of neurotoxin exposure, presenting clinical signs and symptoms and radiological findings are significant in making the diagnosis. Early recognition is crucial and can help optimize patient’s recovery and prevent severe complications.