Background Dopamine D2 receptor agonists, bromocriptine and cabergoline, are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia. An affiliation was found between the initiation of myocardial injury ailment and long term treatment with dopamine D2 agonist drugs identified with the partial activation of 5-hydroxytryptamine receptor 2 A (5-HT2A). The investigation aimed to examine the activity of sarpogrelate (a 5-HT2A receptor blocker) in reducing myocardial injury prompted by extended haul utilisation of D2 receptor agonists in rats with alloxan-induced diabetes. Methods Both bromocriptine and cabergoline were managed independently and combined with sarpogrelate for about a month in diabetic nephropathy rats. Both tail-cuff blood pressure and the BGL were recorded weekly. For all animals, the kidney hypertrophy index, serum creatinine, blood urea nitrogen, alanine transaminase, and aspartate transaminase levels were measured after one month of treatment. The severity of the cardiac injury was assessed by the estimation of lactate dehydrogenase-1 (LDH-1), cardiac troponin I, and tumor necrosis factor alpha 1 (TNF1). The triphenyltetrazolium chloride (TTC) staining method was used to determine the experimental myocardial infarction (MI) size. Results Bromocriptine and cabergoline created a significant reduction in BGL, BP, and kidney hypertrophy index in diabetic nephropathy rats. Administration of bromocriptine and cabergoline, alone, or in combination with sarpogrelate fundamentally diminished the blood concentrations of alkaline phosphatase (ALP), Aspartate aminotransferase (AST), urea, and creatinine. Bromocriptine and cabergoline alone showed a noteworthy increase in the LDH-1, Troponin I, and TNF1 levels in the serum (p < 0.05). Paradoxically, utilising bromocriptine or cabergoline with sarpogrelate treatment altogether decreased the levels of the myocardial biomarkers in the serum. A mix of bromocriptine or cabergoline with sarpogrelate diminished the level of the myocardial infarct size in the heart assessed through the TTC staining method. Conclusions The examination demonstrated that the combined use of sarpogrelate with bromocriptine or cabergoline decreased the potential adverse effects of these two drugs on the myocardial tissues.