A novel biotechnological approach to the preparation of Ir-doped luminescent silica-based nanostructures is proposed availing use of diatoms microalgae which generate highly nanostructured biosilica shells (frustules) by in vivo biomineralization of orthosilicic acid. After the in vivo incorporation of a phosphorescent organometallic complex (Ir-1) in Thalassiosira weissflogii diatom frustules (DFs), bulk functionalized phosphorescent silica-based nanostructures are obtained by isolation and proper ultrafine processing of Ir-1-doped DFs. High-resolution characterization reveals the presence of phosphorescent hybrid organic/inorganic clusters composed of biogenic silica NPs intimately trapped within the diatom organic residual matter. The biofactory strategy investigated herein can be a sustainable, cost-effective, and scalable route to transition metal-doped silica nanomaterials and can pave the way to a great variety of heavy-metal and rare-earth metal doped silica nanostructures, whose applications range from photonics to imaging, sensing, and biomedicine.