Ganoderma lucidum extract (GE) exhibited excellent antioxidant activity with a diverse range of bioactive constituents for enhancing the antioxidant status in animals. However, the challenge is intestinal-targeted delivery. Microencapsulation is widely employed to protect pharmacological substances by fabricating microcapsules. This study investigated the preparation of multilayer microcapsules. Sodium alginate (SA) was used as the primary wall followed by the creation of polyelectrolyte multilayers using chitosan (CS)-SA to obtain GE/SA-CS. GE had high levels of ergosterol, flavonoids, and triterpenoids as well as >80% of antioxidant properties. In vitro simulated digestion indicated that the multilayers of SA-CS displayed a great controlled release ability under intestinal conditions (82.15 ± 3.99%). SA-CS not only protected the constituents of GE from acid, bile, trypsin, and heat treatment but also extended the storage shelf life of GE. Thus, the development of microencapsulation based on the antioxidant delivery system in multilayer SA-CS microcapsules could retain active compounds in GE.