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<i>Plumeria rubra</i> (L.) is a traditional folkloric medicinal herb used to treat cardiovascular disorders. The present investigation was methodically planned to investigate the pharmacological foundations for the therapeutic effectiveness of <i>P. rubra</i> in cardiovascular illnesses and its underlying mechanisms. Ex vivo vaso-relaxant effects of crude leaf extract of <i>P. rubra</i> were observed in rabbit aorta ring preparations. Hypotensive effects were measured using pressure and force transducers connected to the Power Lab data acquisition system. Furthermore, <i>P. rubra</i> displayed cardioprotective properties in rabbits when they were exposed to adrenaline-induced myocardial infarction. In comparison to the intoxicated group, the myocardial infarction model showed decreased troponin levels, CK-MB, LDH, ALT, ALP, AST, and CRP, as well as necrosis, apoptosis, oedema, and inflammatory cell enrollment. <i>P. rubra</i> has revealed good antioxidant properties and prolonged the noradrenaline intoxicated platelet adhesion. Its anticoagulant, vasorelaxant, and cardioprotective effects in both in vivo and ex vivo investigations are enabled by blocking L-type calcium channels, lowering adrenaline, induced oxidative stress, and tissue tear, justifying its therapeutic utility in cardiovascular disorders.