The aim of the present study was to investigate the protective role of Ginkgo biloba L. leaf extract against the active agent of Roundup® herbicide (Monsanto, Creve Coeur, MO, USA). The Swiss Albino mice were randomly divided into six groups, with each group consisting of six animals: Group I (control) received an intraperitoneal injection of dimethyl sulfoxide (0.2 mL, once only), Group II received glyphosate at a dose of 50 mg/kg of body weight, Group III received G. biloba at a dose of 50 mg/kg of body weight, Group IV received G. biloba at a dose of 150 mg/kg of body weight, Group V received G. biloba (50 mg/kg of body weight) and glyphosate (50 mg/kg of body weight), and Group VI received G. biloba (150 mg/kg of body weight) and glyphosate (50 mg/kg of body weight). The single dose of glyphosate was given intraperitoneally. Animals from all the groups were sacrificed at the end of 72 hours, and their blood, bone marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and glutathione (GSH) levels and the presence of micronucleus (MN), chromosomal aberrations (CAs), and pathological damages. The results indicated that serum AST, ALT, BUN, and creatinine levels significantly increased in mice treated with glyphosate alone compared with the other groups (P<.05). Besides, glyphosate-induced oxidative damage caused a significant decrease in GSH levels and a significant increase in MDA levels of the liver and kidney tissues. Moreover, glyphosate alone-treated mice presented higher frequencies of CAs, MNs, and abnormal metaphases compared with the controls (P<.05). These mice also displayed a lower mean mitotic index than the controls (P<.05). Treatment with G. biloba produced amelioration in indices of hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity relative to Group II. Each dose of G. biloba provided significant protection against glyphosate-induced toxicity, and the strongest effect was observed at a dose of 150 mg/kg of body weight. Thus, in vivo results showed that G. biloba extract is a potent protector against glyphosate-induced toxicity, and its protective role is dose-dependent.