Dantrolene, an FDA approved drug to treat malignant hyperthermia and muscle spasm, has been demonstrated to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediated toxicity of host cells. Ryanodine receptor overactivation and associated disruption of intracellular Ca2+ homeostasis play important roles in SARS-CoV-2 infection and replication of host cells. Dantrolene, as an inhibitor of RyRs, is expected to ameliorate these detrimental effects of SARS-CoV-2 in host cells. Additionally, dantrolene has also been shown to inhibit multiple cell or organ damage induced by hypoxia/ischemia, mitochondria damage, oxidative stresses, inflammation, impairment of autophagy and apoptosis, etc., which are often the causes of severity and mortality of COVID-19 patients. We have repurposed that dantrolene has a high potential at treating COVID-19 patients and reducing its morbidity and mortality.