This study investigates the protective effects of Caffeic Acid Phenethyl Ester (CAPE) against Cyclosporine A (CsA)-induced nephrotoxicity. CsA is a potent immunosuppressive agent commonly used after organ transplantation but has significant nephrotoxic effects, which limit its widespread use. CAPE, a natural compound with strong antioxidant and anti-inflammatory properties, has been shown to reduce oxidative damage in various tissues. Materials and Methods: Wistar-albino female rats were divided into four groups: Control (saline only), CAPE (10 μmol/kg/day for 11 days), CsA (15 mg/kg/day for 10 days), and CsA + CAPE. Biochemical analyses included measurements of blood urea nitrogen (BUN), creatinine (Cr), lipid peroxidation (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activities. Results: CsA administration significantly increased BUN and creatinine levels, indicating renal impairment. The CsA + CAPE group showed reduced creatinine levels comp