Chronic kidney disease (CKD) is becoming a major public health problem worldwide. This study aimed to explore whether peanut skin extract (PSE) has protective effects against high-fat and high-fructose (HF) diet-induced kidney injury. Rats were fed HF diet in the whole experiment, while rats in PSE-treated groups were supplemented with PSE. Finally, PSE reduced kidney tissue weight, perinephric fat weight, and levels of serum ammonia, creatinine, and urea nitrogen, along with decreases of renal IL-1β and TNF-α level. Histological examination indicated that PSE alleviated renal tubular dilatation, and degeneration and partial exfoliation of renal tubular epithelial cells. In addition, PSE decreased serum and urinary uric acid level, together with reductions of XOD production and XOD activity both in serum and liver, and down-regulated expressions of renal NLRP3 and ERS proteins. Thus, PSE may be a potential functional food for protecting against renal injury in high energy intake.