Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common hereditary disorder characterized by progressive renal cyst formation and extrarenal manifestations. While neurological complications such as intracranial aneurysms and hypertensive encephalopathy are recognized, acute leukoencephalopathy remains an extremely rare presentation. This case report discusses a 38-year-old male presenting with acute neurological symptoms, including hemiparesis, dysarthria, and encephalopathy, ultimately diagnosed as ADPKD with uremic leukoencephalopathy. Neuroimaging revealed bilateral white matter abnormalities suggestive of acute leukoencephalopathy. The patient’s condition improved significantly after initiation of hemodialysis, highlighting the reversibility of metabolic encephalopathy in ADPKD. This report underscores the importance of recognizing atypical neurological symptoms in ADPKD patients, emphasizing the need for early diagnosis and timely intervention to prevent long-term complications.