Graphical abstract Highlights • Six new clerodane diterpenoids were isolated from Casearia kurzii. • The structures including absolute configurations were established. • The cytotoxicities to three human cancer cell lines were evaluated. • Some diterpenoids showed strong cytotoxic activities. • Apoptosis and cell cycle arrest of 1 were investigated. Abstract A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new clerodane diterpenoids, designated as kurzipenes A–F (1 – 6), from the leaves of Casearia kurzii. Their structures were elucidated on the basis of NMR spectroscopic data analysis and the absolute configurations were confirmed by the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The cytotoxic activities of compounds 1 – 6 were evaluated against human lung cancer A549 cell line, human cervical cancer Hela cell line, and human hepatocellular carcinoma HepG2 cell line. Most diterpenoids showed potent cytotoxicities against the three selected cancer cell lines. The preliminary mechanism studies revealed that the most active compound 2 , with an IC 50 value of 5.3 μM against Hela cells, induced apoptosis and arrested the Hela cell cycle at the G0/G1 stage to exert cytotoxic effects. [ABSTRACT FROM AUTHOR]