A major global public health concern is chronic renal disease (CRD). Thus, it is necessary to search for beneficial and helpful medications that can stop CRD from progressing to end-stage renal failure. The purpose of this study was to evaluate how erlotinib and garcinia cambogia alleviate the harmful effects of adenine on the rat’s kidneys. Forty animals were divided into four groups: Control group: received normal vehicle, adenine group: received orally (50 mg/kg/day) that is subdivided into 3 groups: adenine group, garcinia cambogia (GC) group: received orally GC (200 mg/kg/day)+adenine, and erlotinib (E) group: received 80 mg/kg/day + adenine. Antioxidant biomarkers and renal function tests were evaluated. Histopathological scoring of tubular damage and renalfibrosis as well as immunohistochemistry evaluation of Bcl2 and p53 expression in the kidneys were performed. In renal tissue, the concentrations of transforming growth factor-1, pERK1/2, and pSTAT3 were assessed. The group that received adenine treatment had considerably higher blood urea nitrogen and serum creatinine levels as well as significant pathological alterations as tubular injury and infltration of infammatory cells. Elevated TGF1, pERK1/2, and pSTAT3 levels were also present. Bcl-2 levels were down while p53 levels were up. All of the detected adenine-induced biochemical and histological alterations were reduced by erlotinib and Garcinia cambogia.We concluded that oral administration of erlotinib and garcinia cambogia may be able to reduce the destructive effects of CRD that may be brought on by their anti-fibrotic, antioxidant, and antiapoptotic pathway capabilities.