Investigation of the fruits of Schisandra sphenanthera led to the isolation of two new dibenzocyclooctadiene lignans, methylgomisin O (1) and chloromethyl schisantherin B (2), together with twelve known lignans (3 - 14). Their structures were elucidated by using extensive spectroscopic techniques including 1D and 2D NMR spectra. Compound 2 was identified as a cyclooctadiene moiety substituted with a chloromethyl group, which is rarely found in natural products, especially in terrestrial higher plants. Among these isolates, compounds 1 and 7 exhibited considerable inhibitory activity against tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production, and did not display any cellular toxicity against RAW264.7 cells. Graphical Abstract New Dibenzocyclooctadiene Lignans from Schisandra sphenanthera and Their Proinflammatory Cytokine Inhibitory Activities