A chemical investigation on the aerial parts of Euphorbia neriifolia led to the identification of thirteen undescribed diterpenoids, phorneroids A–M, including ent-abietane (A–D), ent-kaurane (E–G), ent-atisane (H–K), and ent-isopimarane (L and M) types, together with three known compounds. Phorneroid A represents the first example of 8-spiro-fused 9,10-seco-ent-abietane diterpenoid lactone featuring a unique 6/5/6/5 spirocyclic framework. Biological assays showed that some of the compounds displayed moderate cytotoxicity against two human tumor cell lines, A549 and HL-60.