Sialidases are key virulence factors that remove sialic acid from host cell surface glycans, thus unmasking receptors to facilitate bacterial adherence and colonization. In this study, we report the isolation and characterization of novel inhibitors of the Streptococcus pneumoniae sialidases NanA, NanB, and NanC from Myristica fragrans seeds. Of the isolated compounds (1-12), malabaricone C showed the most pneumococcal sialidases inhibition (IC50 of 0.3μM for NanA, 3.6μM for NanB, and 2.9μM for NanC). These results suggested that malabaricone C and neolignans could be potential agents for combating S. pneumoniae infection agents.