Fifteen new and rare iridoid glucoside dimers, cornusides A–O (1–15), and 10 known iridoid glucosides (16–25) were isolated from the fruit of Cornus officinalis. These new chemical structures were established through spectroscopic analysis (UV, IR, HRESIMS, 1D and 2D NMR). Compounds 1–25were tested for their inhibitory activities by measuring IL-6-induced STAT3 promoter activity in HepG2 cells, and 3, 12, 17, 22, and 23showed inhibitory effects, with IC50values of 11.9, 12.2, 14.0, 7.0, and 6.9 μM, respectively.