In a phytochemical investigation of the whole plant of Euphorbia glomerulans, 17 new (1-17) and five known jatrophane diterpenoids (18-22) were identified. The X-ray crystallographic data of compounds 1, 4, and 21 permitted the definition of the absolute configurations of these compounds. The cytotoxicity and multidrug resistance reversal activities of the 17 new compounds were evaluated on multidrug-resistant MCF-7/ADR cells overexpressing P-glycoprotein. Several compounds showed different chemoreversal activities and considerably decreased cytotoxicity. Compounds 11 (IC50 value of 5.0 ± 0.8 μM) and 12 (IC50 value of 5.2 ± 2.0 μM) possessed MDR reversal activities that were as good as that of verapamil (IC50 value of 4.7 ± 0.6 μM).