DRESS syndrome is a severe cutaneous drug reaction characterized by fever, lymphadenopathy, hematologic abnormalities, multisystem involvement, and viral reactivation. Reslizumab, a monoclonal anti-interleukin-5 antibody, may be considered in the management of DRESS syndrome. In this study, we report two cases of DRESS syndrome successfully treated with reslizumab. A 30-year-old male, who had been taking allopurinol for a month presented to our clinic with generalized erythematous patches that appeared a week ago. Additionally, a 39-year-old female, who had been taking several medicines, including carbamazepine, was referred to our clinic with erythematous patches on her face, trunk, and extremities appearing 10 days ago. In both cases, based on the history of medication usage and European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples criteria, DRESS syndrome was diagnosed. Eosinophilia and systemic symptoms aggravated despite intravenous corticosteroid administration, however, they improved after intravenous reslizumab injection. These cases indicate that DRESS syndrome, which could not be treated with corticosteroids, could be successfully managed with reslizumab.