Sulforaphane-loaded nanoparticles (NP-SF) were prepared in this study to improve their biological effects. Based on propylene glycol alginate and zein as wall materials and anthocyanin and CaCl2 as crosslinking agents, the NPs were encapsulated by the crosslinking method and freeze-dried. With the increasing contents of anthocyanin and Ca2+, the encapsulation efficiency and loading capacity of NP-SF were both increased. In vitro simulated digestion experiments showed controlled release of SF from the NPs. The pharmacokinetics confirmed that NP-SF exerted a slower release effect in rats, with improved SF bioavailability and protective effects on liver injury induced by N-diethylnitrosamine in mice. NP-SF reduced serum indicators of liver injury, increased the activities of antioxidant enzymes and GSH levels, and reduced malondialdehyde levels in the liver. In addition, SF activated the Keap1/Nrf2 signaling pathway and upregulated the expression of the Nrf2 downstream genes NQO1 and heme oxidase 1. High doses of NP-SF, in particular, had a higher therapeutic effect. In conclusion, encapsulation enhanced the biological activity of SF and promoted physiological function.