Diospyros bipindensis (Gürke) stem barks are used in Cameroon by pygmies Baka for the treatment of pulmonary diseases. A common process in all of these diseases is inflammation. Thus, we used the inhibition of NF-κB as a target. Bioassay-guided fractionation was performed on the active dichloromethane extract. A C18 reverse solid phase column was used to fractionate the extract in 5 fractions. Active fractions 3 and 4 were further separated by semi-prep HPLC to afford 4-hydroxy-5-methylcoumarin, plumbagin, canaliculatin, ismailin and betulinic acid as the main constituents. Plumbagin and ismailin inhibited NF-κB with an IC50 of 0.9 and 29.5µM, respectively. Together with minor compounds, they could contribute to the anti-inflammatory activity of the extract. These results may support the traditional use of Diospyros bipindebsis for the treatment of pulmonary diseases.