Renal ischemia‐reperfusion (IR) injury is one of the most common causes of acute kidney injury. We investigated the effects of captopril (CAP), telmisartan (TEL), and bardoxolone methyl (BM) in animals with renal IR injury. Adult male Wistar‐Albino rats were divided into six groups: control, vehicle, IR, IR with CAP, IR with TEL, and IR with BM. Before IR was induced, drugs were administered by oral gavage. After a 60‐min ischemia and a 120‐min reperfusion period, bilateral nephrectomies were performed. Serum urea, creatinine, neutrophil gelatinase‐associated lipocalin (NGAL) levels, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), asymmetric dimethylarginine (ADMA) levels, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH‐Px) activity were measured. Tissue mRNA expression levels of peroxisome proliferator‐activated receptor‐ɣ (PPAR‐ɣ), nuclear factor erythroid 2‐related factor 2 (Nrf2), and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) were analyzed. In addition, renal tissues were evaluated histopathologically and immunohistochemically. All tested drugs reduced renal damage, apoptosis, urea, creatinine, NGAL, TOS, nitric oxide (NO), and ADMA levels, NF‐κB, inducible nitric oxide synthase (iNOS), and endothelin‐1 (ET‐1) expressions (P < 0.001). All tested drugs increased SOD activity, GSH‐Px activity, TAS levels, TT levels, endothelial nitric oxide synthase (eNOS) expression, dimethylarginine dimethylaminohydrolases (DDAHs) expression, Nrf2 expression, and PPAR‐ɣ expression (P < 0.001, P < 0.003). Our results suggest that CAP, TEL, and BM pretreatment could reduce renal IR injury via anti‐inflammatory, antioxidant, and anti‐apoptotic effects. This article is protected by copyright. All rights reserved.