The emergence of drug-resistant influenza viruses and the threat of pandemics highlight the need for new and effective antiviral agents. In this study, we describe the isolation of 3 new (1–3) and 10 known (413) curcuminoids from a methanol extract of Curcuma longa L. All compounds had strong inhibitory effects on the neuraminidases from two influenza viral strains, H1N1 and H9N2, as noncompetitive inhibitors with IC50 values ranging from 6.18 ± 0.64 to 40.17 ± 0.79 lg/ml and 3.77 ± 0.75 to 31.82 ± 1.33 lg/ml, respectively. Compounds 4, 5, and 13 also exhibited significant inhibitory activity against the neuraminidases from novel influenza H1N1 (WT) and oseltamivir-resistant novel H1N1 (H274Y mutant) expressed in 293T cells. Our results suggest that the curcuminoids from C. longa may be potential supplemental molecules in the prevention and treatment of disease by influenza viruses. 2012 Elsevier Ltd. All rights reserved.