Enterovirus 71 (EV71) infection gave a hard hit on young children because of fatal complication, brainstem encephalitis with pulmonary edema. Severe EV71 infections highlights an urgent necessity for the novel antivirals development and repurposing of effective products for medical use. Drugs target specific steps in cycle of viral replication and the modification of existing factors of EV71 immunopathogenesis decipher current approaches for developing antivirals. In addition to chemical compounds, identify active constituents and explore the underlying mechanisms of antimicrobial peptides and natural products may substantiate against EV71 activities to provide pharmacological benefits.