Conotoxins or conopeptides are small disulfide-bridged peptides from venom of cone snails (Conus). Numerous conopeptides show high potency and specificity for a range of important physiological targets including various receptors, ion channels and transporters etc. Each cone snail species produces various and different peptides for prey capture. Conotoxins have been confirmed as attractive neuropharmacological probes, potential drug leads, or as drugs themselves indeed. There are less than 0.1% of this diverse peptide library examined. Therefore, conotoxins are recognized as “Marine Drugs Treasure” and “Untapped Vault”, which provide a rich source of potential drug leads or neurophysiological probes. Among various conotoxins, α-families (α*-conotoxins) target nicotinic acetylcholine receptors (nAChRs) including family α-, αA-, αB-,αC-, αD-, αO-, and αS-conotoxins. The nAChRs are pentameric ligand-gated cationic channels with many subtypes, which are distributed throughout the central and peripheral nervous systems of animals. Structures of nAChR subtypes are highly conserved over a wide species. The nAChRs are very important in the nervous system and verified as key targets for many incurable diseases. Our group discovered a batch of novel α*-conotoxins from South China Sea, which block different subtypes of nAChRs with excellent prospects of new drugs development. Their structures and functions were characterized well, which show great therapeutic effect for intractable neuropathic pain (chronic pain), addiction, depression and cancers etc.