Using proteomics methods, we determined the full sequences of three conodipines (Cdpi-P1, -P2 and -P3). Conodipine-P1-3 have conserved consensus catalytic domain residues, including the Asp/His dyad. The activities of the native Conodipine-Ps were evaluated by conventional colorimetric and by MS-based methods, which provide the first detailed cone snail venom conodipine activity monitored by mass spectrometry. Conodipines can have medicinal applications such inhibition of cancer proliferation, bacterial and viral infections among others.