Detailed phytochemical investigation has been carried out on the bark of Artocarpus elasticus Reinw. ex Blume, which led to the isolation of artonin E (1), a new dihydrobenzoxanthone derivative named elastixanthone (2), cycloartobiloxanthone (3) and artobiloxanthone (4). Structures of these compounds were elucidated on the basis of various spectroscopic (UV, IR, ID-NMR and 2D-NMR) and MS data. Compounds 1-3 displayed outstanding scavenging activity for 1,1-diphenylpicrylhydrazyl (DPPH) with IC5o values of 11.5, 21.6 and 40.0 μg/mL, respectively. In addition, compounds 1-3 displayed broad spectrum antimicrobial activities against thirteen different bacterial strains when tested using the disc diffusion assay. Cytotoxic screening revealed that artonin E (1). constantly exhibited strong cytotoxic activity against human estrogen receptor (ER+) positive breast cancer (MCF-7) and human estrogen receptor (ER-) negative (MDA-MB 231) cells in comparison with the other two, with IC50 values of 2.6 and 13.5 μg/mL, respectively, without being toxic towards the WRL68 (human normal liver) cell line (IC50 value more than 30 [μg/mL). However, the compound was inactive against HepG2 (human liver carcinoma) cancer cells.