Drug nanocarriers based on nanostructured materials are very promising for precision and personalized medicine applications. Diatomite porous biosilica has been recently proposed as a novel and effective material in formulations of drug systems for oral and systemic delivery. In this paper, the cytotoxicity of hybrid diatomite silica functionalized nanovectors is assessed in vivo in a living model organism, the cnidarian freshwater polyp Hydra vulgaris. Hydra specimens are exposed to modified diatomite nanoparticles by prolonged incubation within their medium. Uptake and toxicological effects on Hydra are examined from viability and genetic points of view. High concentrations, up to 3.5 g L−1 for 72 h, of diatomite modified nanoparticles do not affect Hydra morphology nor do growth rate and the genetic analysis confirm the biosafety of this material, opening the way to new applications in nanomedicine.