The quest for bioactives that confer protection against chemotherapy induced cardio toxicity is a front-line area of cardio oncology research. Species of genus Morchella have been used in traditional medicine to treat asthma, wound healing, cough, cold, indigestion, excessive phlegm and breathlessness. M. esculenta, commonly known as guchhi in India is a highly prized culinary morel mushroom. Recent studies carried out in our laboratory have demonstrated significant cardioprotective effect of M. esculenta against doxorubicin (DOX)-induced cardiotoxicity. Since bioactive extracts of morel mushrooms were found to possess profound antioxidant activity, the possible interference of these extracts with antineoplastic activity of chemotherapy drugs is often surmised. The current study was undertaken to evaluate the effect of two anticancer drugs, DOX and cyclophosphamide (CP) on solid tumor-bearing mice treated with bioactive extract of M. esculenta. Solid tumor was induced by subcutaneous injection of Dalton's lymphoma ascites (DLA) cells on the right hind limbs of Swiss albino mice. Animals were administered with various concentrations of methanol extract (ME) of M. esculenta following tumor induction. Tumor growth (volume and mass) was measured for four weeks after tumor induction. Cardioprotective effect of methanolic extract was assessed by determining cardiac injury markers levels in serum, antioxidant status in myocardium and histopathology of heart tissue. The results showed significant cardioprotective effect of ME of M. esculenta on tumor-bearing mice. The findings also suggest that ME of M. esculenta did not delimit the therapeutic effect of DOX and CP despite its profound antioxidant activity.