When administered intravenously, active targeting of drug nanocarriers (NCs) improves biodistribution and endocytosis. Targeting may also improve NC oral delivery to treat gastrointestinal (GI) pathologies or for systemic absorption. However, GI instability of targeting moieties compromises this strategy. This study explores whether encapsulation of antibody-coated NCs in microcapsules would protect against gastric degradation, providing NC release and targeting in intestinal conditions. Nanoparticles coated with antibodies against intercellular adhesion molecule-1 (anti-ICAM) or nonspecific immunoglobulin G (IgG) are encapsulated in chitosan (shell) - alginate (core) microcapsules. Encapsulation efficiency is >95% and NC relase from microcapsules in storage is <10%. There is minimal NC release at gastric pH (<10%) and burst release at intestinal pH (75%-85%). Encapsulated NCs afford increased protection against degradation (threefold to fourfold) and increased cell targeting (8-20-fold) after release versus the nonencapsulated NCs. Mouse oral gavage shows that microencapsulation provides 38%-65% greater protection of anti-ICAM NCs in the GI tract, 40% lower gastric retention, and fourfold to ninefold enhanced intestinal biodistribution versus nonencapsulated NCs. Therefore, microencapsulation of antibody-targeted NCs may enable active targeting strategies to be effective in the context of oral drug delivery.