Antamanide is a non toxic cyclic decapeptide isolated from Amanita phalloides. It antagonizes in vitro and in vivo the phallotoxins, the toxic components of this fungus. It forms complexes of high stability with metal ions, especially with Na⁺. In particular, the selectivity for Na⁺ over K⁺ seems to be fundamental requirement for the cytoprotective activity of antamanide and its analogues. The similarity of the effects induced by the phallotoxin phalloidin and the toxic cancer-produced polypeptide prompted us to investigate on the possible anticancerogenic activity of antamanide. We synthesized and tested a series of linear and cyclic antamanide analogues modified in position 6 or 9 with Gly or Tyr residue. Our experiments demonstrated a cytotoxic and/or cytostatic action for antamanide and some of its synthetic analogues. Due to the different ability of antamanide and of its analogues to exhibit antitoxic and/or anticancerogenic activity, these pharmacological effects may be ascribed to different mechanisms.