Previous studies reported that Pulicaria somalensis (Asteraceae) and related members of this family have long been used in folk medicines and because of its antioxidant activity, has an effective role in protection of biomarkers of cardiac and renal dysfunction. The aim of the present study was to evaluate the protective effects of Pulicaria somalensis mthanolic extract (PSME) on carbon tetrachloride (CCl4)-induced changes in cardio-and nephro-toxicity. For the cardio-protective activity, biochemical parameters such as LDH, creatine kinase and albumin in serum, total protein, MDA and NP-SH levels in myocardial tissues were estimated. For the evaluation of nephro-protective activity, biochemical parameters such as creatinine, urea, uric acid, sodium, potassium and calcium in serum, total protein, MDA and NPSH levels in renal tissues were assesed. The results of the present finding showed a significant (P<0.01-0.001) protection of cardiac and renal biochemical markers in serum and tissues, at both the doses of PSME (250 and 500 mg/kg). The cardiac and renal protective markers were further confirmed by the histopathological examination of cardiac and renal tissues. On the basis of present findings, it can be concluded that CCl4- intoxication induced cardiac and renal biochemical markers dysfunction reversed by the PSME treatment. Keywords: Pulicaria somalensis, cardioprotective, nephroprotective, Carbon tetrachloride, Histopathology