Paracetamol (APAP-Acetaminophen) has been used extensively as antipyretic drug. The purpose of this study was to evaluate the ameliorative role of silymarin or/and Nigella sativa extract against APAP-induced hyperlipidemia in male mice at the biochemical, levels. The mice were divided into seven groups (10/group). The first group was served as control. While, the second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and Nigella sativa extract alone respectively, the fifth and sixth groups were treated with combination of APAP with silymarin and APAP with Nigella sativa extract respectively. The seventh group was treated with combination of both ameliorative compounds (Silymarin and Nigella sativa extract) with APAP and all animals were treated for a period of 30 days. Exposure to APAP at the treated dose to mice led to an alternation of lipid function parameters, increase the TG, total cholesterol, LDL and vLDL levels, decreased HDL level as well as decreased SOD and CAT, while increasing MDA in heart tissues homogenates in APAP treated group. The effects of APAP on the biochemical parameters of mice were dose-dependent. Administration of silymarin or/and Nigella sativa extract to APAP-treated mice alleviate the toxicity of APAP, and this appeared clearly by biochemical improvement of lipid profile picture. But, the alleviation is more pronounced with the both antioxidants. Thus, the pronounce effect of silymarin and Nigella sativa extract is most effective in reducing the toxicity induced by APAP and improving the lipid profile of male mice.