The present study intended to explore the preventive effects of Pueraria lobata leaves against doxorubicin (DOX)-induced myocardial infarction (MI) in Wistar rats. The rats were separated into four groups, with each group containing six rats. Group I control rats; group II received DOX-alone in six equivalent injections for 2 weeks; group III received DOX as abovementioned with P. lobata oral administration for 2 weeks; group IV received P. lobata alone for 2 weeks. At the end of the experiment, postcervical dislocation and MI induced by DOX were determined on the basis of the variations in the animal body and heart weight and further instabilities in cardiac marker enzymes aspartate transaminase, lactate dehydrogenase, creatine kinase, creatine kinase-myoglobin binding, and cardiac troponin I in the serum. At the same time, for group III animals, which were exposed to P. lobata, all the above-denoted marker levels were maintained. Levels of some crucial heart-binding proteins like heart fatty acid binding protein, monocyte chemoattractant protein-1, and transforming growth factor beta were elevated in DOX-alone treated rats. Additionally, group III animals treated with P. lobata showed some preventive downregulated expressions of these binding proteins. Histopathological observations also revealed the preventive effect of P. lobata. Ultimately proteins tangled in the phosphoinositide 3-kinase/protein kinase B pathway were studied by Western blot. P. lobata treatment downregulated the inflammatory markers. The findings suggest that P. lobata exhibits cardioprotective effect on MI.