Many　herbal　medicines　and　compositions　are　clinically　effective　but　challenged　by　its　safety　risks,　i.e.,　aconitine　(AC)　from　aconite　species.　The　combined　use　of　Radix　glycyrrhizae　(licorice)　with　Radix　aconite　L.　effectively　eliminates　toxicity　of　the　later　while　increasing　efficacy.　In　this　study,　a　boiling-stable　31-kDa　protein　(namely　GP)　was　purified　from　licorice　and　self-assembled　into　nanoparticles　(206.2　±　2.0 nm)　at　pH　5.0,　25 °C.　The　aconitine-encapsulated　GP　nanoparticles　(238.2　±　1.2 nm)　were　prepared　following　the　same　procedure　and　tested　for　its　toxicity　by　intraperitoneal　injection　on　ICR　mouse　(n　=　8).　Injection　of　GP-AC　nanoparticles　and　the　mixed　licorice-aconite　decoction,　respectively,　caused　mild　recoverable　toxic　effects　and　no　death,　while　the　aconitine,　particle-free　GP-AC　mixture　and　aconite　decoction　induced　sever　toxic　effects　and　100 %　death.　Encapsulation　of　poisonous　alkaloids　into　self-assembled　herbal　protein　nanoparticles　contributes　to　toxicity　attenuation　of　combined　use　of　herbs,　implying　a　prototype　nanostructure　and　a　universal　principle　for　the　safer　clinical　applications　of　herbal　medicines.　©　2015,　Ke　et　al.