Acetaminophen (APAP) is a well‐known drug that, in high doses, induces hepatotoxicity and nephrotoxicity. This study has investigated the preventive effect of the extract and fractions of Ribes khorasanicum on APAP‐induced liver and kidney damage. In this experiment, after analysis of the extract using FTIR, toxicity was induced by APAP on the 7th day. Before that, the extract and their aqueous, ethyl acetate, and n‐hexane fractions were administrated orally. 24 h after APAP administration, the animals were sacrificed. The liver and kidney were removed for the evaluation of oxidation and biochemical markers, including SGOT, SGPT, ALP, LDH, albumin, urea, creatinine, and bilirubin and also for histopathological evaluations. The safety of the extract was evaluated based on the MTT. Also, expression of the NF‐kB is done. Administration of Ribes khorasanicum significantly decreased the biochemical parameters compared to the APAP. Oxidative parameters, as well as histopathological changes in preventive groups, were improved compared to the APAP in both tissues. The results showed that the aqueous and ethyl acetate fractions of the extract had a better effect than the whole extract and n‐hexane fraction against APAP toxicity.