This study was aimed at evaluating the preventive role of the ethanolic extract of Lagenaria siceraria (Mol) fruit on membrane-bound enzymes, such as sodium potassium-dependent adenosine triphosphatase (Na+/K+ ATPase), calcium-dependent adenosine triphosphatase (Ca2+ ATPase) and magnesium-dependent adenosine triphosphatase (Mg2+ ATPase) on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with the ethanolic extract of L. siceraria (Mol) fruit (125, 250 and 500 mg kg−1 body weight) for a period of 30 days. After the treatment period, ISO (85mg kg−1 body weight) was subcutaneously injected into rats at 24-h intervals for 2 days. ISO-induced rats showed a significant (p < 0.05) decrease in the activity of Na+/K+ ATPase and an increase in the activities of Ca2+ and Mg2+ ATPases in the heart tissues. Pre-treatment with the ethanolic extract of L. siceraria (Mol) fruit for a period of 30 days exhibited a significant (p < 0.05) effect in ISO-induced rats. Thus, our study shows that the ethanolic extract of L. siceraria (Mol) fruit has membrane-stabilising role in ISO-induced MI in rats.