Cytokine-releasing syndrome (CRS) is a special form of systemic inflammatory response syndrome provoked by factors like viral infections and certain immunomodulatory drugs like monoclonal antibodies and adoptive T therapy. To elucidate the potential role of ramipril (RM) and its combination with methylprednisolone (MP) against the development and progression of CRS in mice. This experiment consists of two parts: protective and therapeutic interventions. The protective experiment: in the induction group, mice received an intraperitoneal injection (IP) of 5mg/kg lipopolysaccharide (LPS) without intervention. The other groups received various drugs before the induction by three days, then observed for an additional two days (50 mg/kg MP, 3 mg/kg RM, and a combination of 1.5 mg/kg RM with 25 mg/kg MP). The second part of the study involves the therapeutic potential; all groups received similar doses of drugs in the prevention groups, except LPS induction was given first, and after one hour, the mice received daily doses of the drugs for five days. At the end of the experiment, blood and tissue samples were obtained. Mice treated with RM and its combination with MP showed improved serum TNF-α, IL-6, IL-8, IL-1β, INF-γ, MDA, and GSH in both prevention and therapeutic groups. Histopathologically, mice treated with ramipril and its combination with MP ameliorate the tissue damage in both lung and liver tissues following LPS induction. Ramipril showed protective and therapeutic effects in LPS-induced cytokine storms in mice through anti-inflammatory and antioxidant mechanisms.