Abstract OBJECTIVE To evaluate the potential contribution of glycyrrhizin (GLZ) to mitigate the testicular toxicity linked to cisplatin (CIS) intoxication. METHODS 40 mature male Wistar albino rats (Rattus norvegicus albinus) were randomly divided into 4 equal groups (n = 10) for 60 days: the control group, CIS-treated group (single dose of 7 mg/kg, IP), GLZ-treated group (25 mg/kg, PO), and GLZ plus CIS–treated group. Blood and testis samples were examined using biochemical, histological, and immunohistochemical techniques. Semen samples were also obtained, and any abnormalities were reported. RESULTS Serum follicle-stimulating hormone, luteinizing hormone, and testosterone levels were all markedly reduced by CIS. Oxidative stress and a signifcant reduction in levels of the antioxidant enzymes glutathione peroxidase, superoxide dismutase, and catalase were linked to CIS. Immunohistochemically, CIS showed difuse, signifcantly positive immunolocalizations against the anti-caspase 3 antibody, indicating widespread apoptosis within the testicular parenchyma. Histopathologically, CIS showed difuse coagulative necrosis of spermatogenic cells, necrotic Sertoli cells, intertubular edema, and Leydig cell hyperplasia. Moreover, CIS revealed a noteworthy increase in sperm abnormalities. Pre-coadministration and posttreatment with GLZ mitigated the majority of these detrimental consequences, and serum levels of antioxidant enzymes, luteinizing hormone, follicle-stimulating hormone, and testosterone were signifcantly elevated. CONCLUSIONS Glycyrrhizin has been proven to be a strong antioxidant as well as antiapoptotic and cytoprotective against CIS testicular damage. CLINICAL RELEVANCE The described model is a tool to evaluate the testicular protective impact of GLZ.