Diclofenac (DIC) (Voltaren) belongs to the non-steroidal anti-inflammatory drug family. It is one of the compounds derived from phenylacetic acid; liver toxicity is one of the main concerns for this drug. The present study investigated the effect of ethanolic extract of ficus sycomorus leaves and fruits against diclofenac-induced oxidative stress and hepatotoxicity in rats. Forty-two male albino rats weighing (150±10 g) were divided into seven equal groups. The first group (6 rats) was fed on a basal diet and served as a negative control. The second group (36 rats) received a single intraperitoneal dose of DIC (150 mg/kg b.w.) at the end of the experimental period. It was divided into six subgroups: Group 1 was fed on a basal diet only and served as a positive control (+v), Group 2 was fed on a basal diet, and silymarin (100 mg/kg b.w., orally). Groups (3&4) were orally fed on a basal diet and ethanolic extract of sycamore fruits (200 and 400 mg/kg b.w.) for 28 days, respectively. Groups (5&6) were fed on a basal diet and sycamore leaves ethanolic extract orally (200 and 400 mg/kg b.w.), respectively. Biological data were calculated at the end of the experiment, and blood samples were taken for biochemical analysis. In addition, liver tissues were analyzed for antioxidant markers, malondialdehyde (MDA), and histological examination was also examined.  The results revealed that the diclofenac group caused an increase in liver weight, serum liver enzymes, liver MDA and NO, and a decrease in serum liver GP_X, SOD, and CAT. All treated groups with fruits and leaves extracts showed improvement in all previous parameters compared with the (+ve) control group. In conclusion, consuming the ethanolic extract of ficus sycomorus leaves and fruits can lower the side effects of the diclofenac toxicant.