In this study, two undescribed compounds (1 and 2), together with eight known compounds (3-10) were isolated from the aerial parts of Piper samentosum by various chromatography methods. Their chemical structures were determined to be 7'''-oxolyciumamide N (1), vitexin 2''-O-β-D-(6'''-feruloyl)-glucopyranoside (2), 1,2-dihydro-6,8-dimethoxy-7-hydroxy-1-(3,4-dihydroxyphenyl)-N1,N2-bis-[2-(-hydroxyphenyl)ethyl]-2,3-napthalene dicarboamide (3), vitexin 6''-O-β-D-glucopyranoside (4), vitexin 2''-O-α-L-rhamnopyranoside (5), methyl 2-hydroxybenzoate-2-O-β-D-apiofuranosyl-(1→2)-O-β-D-glucopyranoside (6), ficuside G (7), methyl 2-O-β-D-glucopyranosylbenzoate (8), methyl 2,5-dihydroxybenzoate-5-O-β-D-glucopyranoside (9), and 3,7-dimethyloct-1-ene-3,6,7-triol 6-O-β-D-glucopyranoside (10) by spectroscopic data analysis including HR-ESI-MS, 1D-, and 2D-NMR spectra. Compounds 1-5 inhibited nitric oxide production in LPS-stimulated RAW264.7 macrophages with the IC50 values of 27.62, 74.03, 38.54, 70.39, and 44.95 μM, respectively. The NMR data of 9 were firstly reported herein.