Euphorbiaceae barks are known to contain an appreciable amount of polyphenolic compounds responsible for several biological activities. Preliminary extraction from Bridelia grandis stem bark afforded high content of polyphenols, determined by spectrophotometric methods such as Folin-Ciocalteu (for total phenols, TP) and n-butanol-HCl (for condensed tannins, CT). A preliminary Plackett-Burman screening design was used to identify the key factors that influence the TP and CT extraction. Between all the variables known to influence the extraction from vegetable matrixes, six were selected; maceration was chosen as traditional extraction methodology. To investigate the effect of solvents and extraction method, methanol, acetone 70% (v/v in water), centrifugation and ultrasound were chosen. A full factorial design 2(3) was applied to optimize the extraction procedure. The responses were obtained analyzing the extracts for their TP and CT contents determined by the above-mentioned spectrophotometric methods. The results confirm that, within the explored domain, the optimum solvent is methanol and the optimum method is one-cycle centrifugation. Finally, it was also compared with the effect of maceration on the considered responses. It has never given results better than centrifugation, whereas in the case of CT it represents an advantage to employ a three-cycle centrifugation instead of one.