The main trigger of kidney failure is free radicals. Our bodies need a compound that can help counteract free radicals or often called antioxidants. Research shows that dragon fruit is rich in antioxidants. This study aims to determine the antioxidant activity of red dragon fruit peel extract (Hylocereus polyrhizus) against cystatin C and Kidney Injury Molecule 1 (KIM-1) in gentamicin-induced wistar rats. This study was an experimental study conducted at the USU Pharmacology Laboratory during October 2022. The experimental animals were divided into 5 treatment groups and each treatment consisted of 5 rats. The test animals were given red dragon fruit peel extract (Hylocereus polyrhizus) at a dose of 100, 200 and 300 mg/kg BW which is an effective dose because it can reduce free radicals. Data were analyzed using the one way Anova test at the 95% level of confidence and for data that were not normally distributed and not homogeneous, the Kruskal Wallis test was used. Dragon fruit ethanol extract at a dose of 300 mg/kgbw can significantly reduce urea and creatinine levels (p<0.05), KIM-1 levels (p<0.05), and cystatin levels significantly (p<0.05) when compared to the group that was given only gentamicin. Dragon fruit extract antioxidants have a good effect on preventing gentamicin-induced kidney deterioratio