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<i>Lindera obtusiloba</i> Blume has several activities, such as anti-inflammatory, anti-allergic, anti-tumor, anti-wrinkle, and antioxidant activities. Interleukin-6 (IL-6) is a classic pro-inflammatory cytokine that is associated with various functions, such as proliferation, invasion, inflammatory responses and functions within antioxidant defense systems. In this study, we investigated IL-6-induced STAT3 activation of lignan compounds isolated from <i>L. obtusiloba</i>. The structures of the isolated compounds were elucidated via spectroscopic nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS). As a result, seven lignans were identified from <i>L. obtusiloba</i>. All the isolated compounds (<b>1</b>–<b>7</b>) were evaluated for their IL-6-induced STAT3 inhibitory effects in Hep3B cells using a luciferase reporter assay. Of the isolates, compounds <b>1</b> and <b>5</b> showed inhibitory effects against IL-6-stimulated STAT3 activation. Furthermore, the mRNA expression levels of inflammation-related genes such as CRP, IL-1b, and SOCS3 were significantly reduced by exposure to compounds <b>1</b> and <b>5</b>. The protein levels of p-STAT3 and p-JAK2 in IL-6-induced U266 cells were regulated in the presence of lignans derived from <i>Lindera obtusiloba</i> by Western blot assay. Based on the results, this study of <i>L. obtusiloba</i> demonstrates that the species has promise as a bioactive candidate for the treatment of IL-6-induced STAT3-related disease.