Objective: To report two cases with anti-GAD antibodies associated neurological disorder in patients with acute leukemia who received standard chemotherapeutic protocols. Clinical presentation and intervention: Case 1: patient with biphenotypic acute leukemia developed motor neurological symptoms while receiving induction therapy. Anti-GAD antibodies were demonstrable in the CSF and serum, and the patient responded to Intravenous Immunoglobulin (IVIG) therapy. Case 2: Patient with relapsed B-Acute lymphoblastic leukemia (ALL) after allogenic stem cell transplant developed progressive neurological symptoms. Anti-GAD65 antibodies were demonstrable in the serum, but not the CSF. The patient did not respond to IVIG and had to be given plasmapheresis and steroids. 2-year follow-up status of both patients is provided. Conclusion: Immunological etiology with Anti-GAD antibodies needs to be considered in the differential diagnosis of central and peripheral neurological illness in acute leukemia patients on standard chemotherapeutic protocol. IVIG is an effective treatment for this condition. However, in case of inadequate or no response, plasmapheresis with steroid or rituximab should be considered. Long-term management is required to prevent and manage relapse of autoimmune neurological illness.