Crotonpenoids A (1) and B (2), two highly modified clerodane diterpenoids featuring a new 10-(butan-2-yl)-1,6,12-trimethyltricyclo[7.2.1.02,7]dodecane skeleton, were isolated from the leaves and twigs of Croton yanhuii. Their structures including the absolute configurations were determined by spectroscopic analysis, single-crystal X-ray diffraction, and biomimetic semisynthesis. Compounds 1 and 2 exhibited an agonistic effect on pregnane X receptor at 10 μM.