Abstract: Background and Objectives: Hypericum perforatum, which have various names locally such as St. John Wort, is a plant which blooms between July and September at farms, borders of roads and woods, top of hills and grasslands, which is regulator of apoptotic mediators are shown in various studies. Also, it is known that gentamicin activates apoptotic mediators and causes necrosis in kidney. Due to this reason, a study was planned to examine the protective effects of Hypericum perforatum on nephrotoxicity caused by gentamicin. Materials and Methods: Mice were divided into three groups; control group, gentamicin group and perforatum extract group. About 100 mg kg–1 gentamicin and 70 mg kg–1 H. perforatum extract are administered to related groups for 9 days. Renal tissue samples and blood samples are obtained for biochemical analysis. caspase-3, bax and bcl-2 proteins are analyzed by using ELISA method. Results: Gentamicin administration increased caspase-3, bax while it decreased bcl-2. H. perforatum administration to mice that are administered gentamicin previously decreased the rate of caspase-3, bax caused by gentamicin while it increased bcl-2. Gentamicin also increased serum BUN, creatinine, TOS and TNF-α levels and renal MDA levels significantly and decreased catalase (CAT) and glutathione (GSH) significantly compared to other groups. Gentamicin+perforatum extract treatment reversed these factors compared to the gentamicin group (p<0.05). Conclusion: Histopathologic examination revealed severe edematous damage gentamicin group and reduced edematous damage in the gentamicin+perforatum extract group. Hypericım perforatum extract provides renal protection against gentamicin-induced nephrotoxicity through its antioxidant and anti-inflammatory effects.