Renal ischemia-reperfusion injury (IRI) makes a significant contribution to delayed graft function (DGF) and reduced allograft survival time post-transplantation, thereby complicating the prognosis of renal transplant recipients. Cordycepin, an active compound purified from the traditional Chinese medicine Cordyceps sinensis, has exhibited remarkable anti-inflammatory and organ-protective effects against various diseases, including neurological, hepatic, and metabolic disorders. Therefore, the present study used a murine model of renal ischemia/reperfusion (I/R) and HK2 cell line hypoxia/reoxygenation (H/R) to determine whether cordycepin influences renal IRI. The findings indicated that cordycepin significantly mitigated renal IRI by inhibiting the p38/JNK signaling pathway in the renal tubular epithelial cells, thereby suppressing inflammation, cell apoptosis, and ferroptosis. These findings offer a novel avenue for improving the prognosis of renal transplant recipients and allograft survival.