Seven previously undescribed diterpenoid alkaloids, eight reaction products and thirteen known compounds were isolated from the whole plant of Delphinium grandiflorum L. (Ranunculaceae). Grandiflonines A and B have an unprecedented C20–diterpenoid alkaloid skeleton, which features inversion of the configuration of C–18. Their structures were determined by comprehensive analyses of spectroscopic data, X–ray diffraction and Mosher's method. The probable biosynthetic pathway of grandiflonine A was discussed. Additionally, the analgesic activity and anti–inflammatory activity by inhibition of NO production were evaluated. Among them, deoxylappaconitine (ED50 = 0.35 mg/kg, TI = 46.22) showed significant analgesic activity that was superior to the reference drug lappaconitine (ED50 = 3.5 mg/kg, TI = 3.34). © 2021 Elsevier Ltd