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Currently, no disease\u2010specific therapies exist to treat viral myocarditis. Here it is examined whether reconstituted, lyophilized extracellular vesicles (EVs) from platelets from healthy men and women reduce acute or chronic myocarditis in male mice. Human\u2010platelet\u2010derived EVs (PEV) do not cause toxicity, damage, or inflammation in na\u00efve mice. PEV administered during the innate immune response significantly reduces myocarditis with fewer epidermal growth factor (EGF)\u2010like module\u2010containing mucin\u2010like hormone receptor\u2010like 1 (F4\/80) macrophages, T cells (cluster of differentiation molecules 4 and 8, CD4 and CD8), and mast cells, and improved cardiac function. Innate immune mediators known to increase myocarditis are decreased by innate PEV treatment including Toll\u2010like receptor (TLR)4 and complement. PEV also significantly reduces perivascular fibrosis and remodeling including interleukin 1 beta (IL\u20101\u03b2), transforming growth factor\u2010beta 1, matrix metalloproteinase, collagen genes, and mast cell degranulation. PEV given at days 7\u20139 after infection reduces myocarditis and improves cardiac function. MicroRNA (miR) sequencing reveals that PEV contains miRs that decrease viral replication, TLR4 signaling, and T\u2010cell activation. 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