Cisplatin is one of the most widely used cytotoxic therapeutic agents for the treatment of cancer. This drug, at effective higher doses or multiple low doses, causes many physiological adverse effects. N,N Diphenyl-р-phenylenediamine (DPPD) and Vit C against cisplatin-induced oxidative stress in rats. Cisplatin was injected once a week (2 mg/kg bwt) for 4 weeks. DPPD (125 mg/kg bwt) and vit C (100 mg/kg bwt) were injected once a week an 24 hour prior to cisplatin injection. In cisplatin treated group, the number of RBCs and WBCs were decreased (P< 0.05) compared to that of control rats. However, in rats injected with Vit C or DPPD prior to cisplatin treatment, blood cells counts elevated again to their normal values. Cisplatin toxicity was manifested biochemically by a significant increase (P<0.05) of LPO in spleen as well as a decrease in GSH content which associated with a reduction in the activities of antioxidant enzymes, SOD, CAT, GST and γ GGT in spleen and plasma. In addition to the marked decrease in Vit C and Vit E levels. In rats treated with Vit C or DPPD in combination with cisplatin LPO and the activities of SOD, GST, CAT and GGT restored to about normal control levels. In conclusion DPPD and vitamin C are efficient promising compounds for reducing cisplatin-toxic side effects.