Ornidazole-induced encephalopathy (OIE) is seldom seen in the clinic. In this study, we report a new case of a patient who had taken 1,000 mg ornidazole daily for nearly 4 years because of suspected diarrhea and proctitis and presented with subacute symptoms such as unsteady gait, slurred speech, and psychiatric disorder. These symptoms were significantly relieved 3 days after the patient stopped taking ornidazole. When he took this medicine again, however, similar symptoms occurred 4 months later, which were again reduced after 4 days of drug discontinuation. After the second onset, abnormal signals were identified around the aqueduct of the midbrain, around the fourth ventricle, and in the dentate nuclei of the cerebellum bilaterally. After 9 days of drug discontinuation, lesions disappeared in the magnetic resonance imaging (MRI) results. According to the clinical manifestations, imaging features, and the reduced symptoms after drug withdrawal, we clinically diagnosed the patient with OIE. This paper also reviews the literature on OIE. Only five cases (including our case) have been reported, all of whom presented with cerebellar ataxia and dysarthria and three with additional mental symptoms such as agitation and irritability. All five patients had abnormal lesions in the dentate nucleus of the cerebellum bilaterally, among whom four also had lesions in the corpus callosum and three around the periaqueduct of the midbrain. After withdrawal of ornidazole, the symptoms in all patients vanished or were alleviated, and three of them showed reduced or disappeared lesions in a head MRI reexamination. Overall, OIE has rarely been reported. Our case report and literature review show that the lesions in the cerebellum, corpus callosum, and brainstem can be reversed. The main manifestations of the lesions-cerebellar ataxia, dysarthria, and mental symptoms-quickly weaken or disappear after drug withdrawal, with good prognosis. Nevertheless, clear pathogenesis has yet to be further investigated.