Caffeine is the major constituent found in coffee, tea, energy drinks, and chocolate bar among many others. Several studies have reported various effects of caffeine on the cardiovascular system, although there are inconsistencies in these findings. This study, based on these sought to investigate the role of Myristica fragrans on caffeine-induced cardiotoxicity in male Wistar rats. Twenty-five healthy Wistar rats, weighing 130-135 g were randomly assigned into groups (A-E) n=5 each. Group A received 2 mL/kg distilled water as placebo, group B was administered caffeine (40mg/kg), group C received Myristica fragrans only (200mg/kg), group D received caffeine (40mg/kg), and Myristica fragrans (100mg/kg), while group E received caffeine (40mg/kg) and Myristica fragrans (200mg/kg). The rats were orally-gavaged caffeine and Myristica fragrans with the aid of an oral cannula for 21 days. On the 22nd day after the last administration, rats were euthanized sacrificed and the heart tissues were obtained histological procedures. Percentage weight change was significantly decreased (p <0.05), and Lactate dehydrogenase (LDH) activity was significantly increased (p <0.05) in group B relative to the control group. The heart, relative heart weights, and cardiac troponin I were not significantly different (p=0.05) across all experimental groups relative to the control. Assessment of the cardiac histoarchitecture revealed diverse alterations in the caffeine-only group which were ameliorated by administration of 100 and 200 mg/kg Nutmeg extract in groups D and E respectively. Caffeine administration resulted in alteration in cardiac histoarchitecture with 100 and 200mg/kg Myristica fragrans ameliorating these alterations. Nutmeg could serve as a drug lead in the management of cardiac-related conditions.