ABSTRACT Dengue virus (DENV) causes millions of infections each year, and there are currently no approved antivirals. Essential oils could serve as potential candidates for developing plant-based dengue treatments. Lippia alba (Mill.) N.E. Brown essential oil (LAEO) was selected to investigate the mode of antiviral action and its effect on activated platelets. Binding affinities of 20 LAEO compounds and platelet proteins were investigated through docking analyses. LAEO showed a potent virucidal effect (IC50, 2.1 to 5.1 μg/mL) against all DENV serotypes. LAEO reduced P-selectin (from 61% to 18%) and increased survival (from 71% to 97%) in DENV-2- and DENV NS1-stimulated human platelets. Sesquiterpene hydrocarbons showed the highest binding affinities (from −7.3 to −8.0 kcal/mol) with platelet innate immune receptors such as TLR2/1, TLR4/MD-2 and αIIbβ3 integrin. The data provide a first step towards defining the potential of LAEO as a candidate for developing phytotherapeutics for dengue.