In the present study it was aimed to evaluate the combined effect of simvastatin (SIM) and hydro alcoholic seeds extract of Lagenaria siceraria (H.L.S.S.E.) in doxorubicin (DOX) induced cardio toxicity in Wister rats. DOX 10 mg/ kg i.p. single dose was given to cause cardiac damage and the levels of cardiac biomarker enzyme viz LDH, CK, CK-MB and total protein & antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and lipid peroxidation (LPO) were observed and in the end of experiment histopathology was carried out for heart. SIM (15 mg/kg) and (H.L.S.S.E. 200 & 400mg/kg) were given in combination with DOX 10 mg/ kg i.p. single dose to rats at the 30th day of experiment and as a pretreatment for 29 days (H.L.S.S.E. 200 & 400mg/kg) were given orally. Pretreatment with SIM and (H.L.S.S.E) significantly (P<0.001) reduced the elevated cardiac toxicity biomarker enzyme level and raised the level of antioxidants viz CAT, GSH, SOD and decrease LPO in the extract treated groups as compared to the disease control group .In the histopathological studies H.L.S.S.E and SIM showed protection against myocardial toxicity induced by doxorubicin. The result obtained from the present study indicates that the pretreatment of SIM and H.L.S.S.E may significantly reduse the (DOX) induced cardiotoxicity.