• Two new polycyclic polyprenylated acylphloroglucinols and seven known analogues were isolated. • Structure elucidation was performed by spectroscopic measurements including 2D-NMR spectroscopy. • Some compounds exhibited cytotoxic and antibacterial activities. Phytochemical investigation of the whole plant of Hypericum curvisepalum led to the isolation of nine polycyclic polyprenylated acylphloroglucinols ( 1 – 9 ). Among them, curvisepalumiones A ( 1 ) and B ( 2 ) are two new compounds and their structures were elucidated based on extensive spectroscopic data analysis combined with Rh 2 (OCOCF 3 ) 4 -induced electronic circular dichroism experiment. Cytotoxic assay showed that all the tested compounds except for 1 was moderately cytotoxic against human hepatocarcinoma cell line SMMC-7721 cell line, while compounds 3 and 4 also exhibited cytotoxicity toward MGC-803 cells. In addition, compound 2 exhibited weak inhibitory activity against Bacillus subtilis .