Three new triterpenoids, cucurbalsaminones A-C (<b>1</b>-<b>3</b>), featuring a unique 5/6/3/6/5-fused pentacyclic carbon skeleton, named cucurbalsaminane, were isolated from a methanol extract of <i>Momordica balsamina</i>. Their structures were elucidated by spectroscopic methods and corroborated, for <b>1</b>, by structure solution using single-crystal X-ray diffraction analysis. A hypothetical biogenetic pathway for these compounds is proposed. Compounds <b>1</b>-<b>3</b> were evaluated for their P-glycoprotein (P-gp/ABCB1) modulation ability, using a mouse T-lymphoma <i>MDR1</i>-transfected cell model by the rhodamine-123 accumulation assay, and displayed potent multidrug resistance (MDR)-reversing activity.