Diatoms are single-celled algae that make silica shells or “frustules” with intricate features patterned at the nano- and microscales. We report that antibody-functionalized diatom biosilica frustules may serve as a biosensor platform to selectively report antibody-antigen immunocomplex formation through enhanced photoluminescence. Biosilica frustules of 10 micron diameter isolated from cultured cells of centric diatom Cyclotella sp. were mounted on glass and then covalently functionalized with the model antibody Rabbit Immunoglobulin G (IgG) to yield a uniform, nanotextured antibody surface that binds selectively to its complimentary antigen, Goat anti-Rabbit IgG. Diatom frustules possess an intrinsic capacity to emit blue light when excited with a UV laser light source, a property called photoluminescence, which is enabled by the nanostructure of the diatom biosilica. Binding of the antibody-functionalized diatom frustule with its complimentary antigen selectively intensified the intrinsic photoluminescence intensity of the diatom biosilica through a nucleophilic enhancement mechanism, whereas challenging the antibody-functionalized diatom frustule with its non-complimentary antigen (Goat anti-Human IgG) did not change the photoluminescence intensity. It was proposed that the nucleophilic immunocomplex increased the PL intensity by donating electrons to non-radiative defect sites on the photoluminescent diatom biosilica, thereby decreasing non-radiative electron decay and increasing the radiative emission, resulting in label-free detection of the complimentary antigen. Consequently, antibody-functionalized diatom frustules hold considerable promise for the standoff detection of target biomolecules.