Ligustilide is a bioactive component of the traditional Chinese herb Angelica sinensis that exhibits analgesic, anti-inflammatory, anticancer, neuroprotection, and anti-atherosclerosis pharmacological activities. Herein, the role of ligustilide in intracerebral hemorrhage-induced cardiac damage has been assessed. An autologous blood injection was used to induce intracerebral hemorrhage in CD-1 mice that resulted in an increase in systolic and diastolic blood pressure. Intraperitoneal administration of ligustilide reduced systolic and diastolic blood pressure, decreased plasma levels of adrenaline and noradrenaline in mice with intracerebral hemorrhage. Also, cardiac injury was observed in mice with intracerebral hemorrhage, as demonstrated by the upregulation of creatine kinase-MB, lactic dehydrogenase, and aspartate transaminase. Moreover, Picrosirius red staining showed cardiac fibrosis in intracerebral hemorrhage mice that was attenuated by ligustilide. Lastly, ligustilide reduced levels of interleukin-1 beta, tumor necrosis factor-a, interleukin-6, and reactive oxygen species in mice with intracerebral hemorrhage. Cardiac apoptosis in mice with intracerebral hemorrhage was also inhibited by ligustilide, as shown by reduced protein expression of phospho-p65, enhanced nuclear factor erythroid 2-related factor 2, and heme oxygenase-1 expression.