Hedyorienoids A (1) and B (2), two sesquiterpenoid dimers, were isolated and characterized from Hedyosmum orientale. Compound 1 was an unprecedented heterodimer of two different classes of sesquiterpenoids furnished by forming an unusual 1,3-dioxolane ring, while compound 2 possessed a new dimerization pattern of two guaiane-type sesquiterpenoids. Biosynthetic pathways for 1 and 2 were proposed with the coexisting monomers chloranthalactone A (3) and hedyosumin A (4) as the precursors. Compounds 2 and 3 showed significant NF-κB inhibitory activity.