Six new ellagitannins, brevipetins B-G (<b>5</b> and <b>7</b>-<b>11</b>), and a new phenolic glucoside, brevipetin A (<b>4</b>), along with six known compounds were isolated from the traditional Chinese medicinal plant <i>Cleidion brevipetiolatum</i>. Their structures and absolute configurations were determined by spectroscopic analyses, chemical methods, and TD-DFT-ECD calculations. Compounds <b>5</b>-<b>11</b> exhibited NO inhibitory effects with IC<sub>50</sub> values of 1.9-8.2 μM, and <b>9</b> showed the most potent inhibitory effect (IC<sub>50</sub>: 1.9 μM). An in vivo anti-inflammatory assessment of <b>9</b> showed that it exerts therapeutic effects in both the carrageenan-induced rat paw edema and collagen-induced arthritis (CIA) models at 50 mg/kg oral administration. The enhanced protein and mRNA expression levels of iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) in LPS-stimulated RAW 264.7 cells were dose-dependently suppressed by <b>9</b>. An anti-inflammatory mechanistic study revealed that <b>9</b> suppressed NF-κB activity by inhibiting IκBα phosphorylation and blocking translocation of p65 from the cytosol to the nucleus. Therefore, <b>9</b> might have the potential to be developed as a lead compound for relieving rheumatoid arthritis.