Renal ischemia-reperfusion injury (IRI) is a critical health concern that aggravates the pathophysiology of acute kidney injury (AKI), leading to high mortality rates in intensive care units. Cardamonin is a natural compound with anti-inflammatory and antioxidant properties. The current study aimed to evaluate the renoprotective impact of cardamonin against AKI induced by renal IRI. Male rats (n=5 per group) were divided into four groups: the sham group underwent anesthesia and abdominal incision only; the control group experienced bilateral renal artery clamping for 30 minutes followed by 2 hours of reperfusion; the vehicle group received the cardamonin vehicle 30 minutes before ischemia induction; and the cardamonin group was administered 5 mg/kg of cardamonin 30 minutes before ischemia. Blood urea nitrogen (BUN) and creatinine were measured to assess the renal function. Tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin-6 (IL-6), caspase 3, and F2-isoprostane were assessed in renal tissues. Kidney injury was examined using the hematoxylin and eosin stain method. Compared to the sham group, the control group exhibited significantly higher levels of BUN, creatinine, TNF-α, IL-1β, IL-6, F2-isoprostane, and caspase 3 in renal tissues, along with severe kidney injury as evidenced by histological analysis. Compared to the control group, pretreatment with cardamonin resulted in a significant reduction in these biomarkers and alleviated renal damage. Cardamonin had renoprotective effects against renal ischemia and reperfusion injury via modulating inflammation, oxidative stress, and apoptosis pathways.