Rapid progress in the development of highly efficient nanoparticle-based construction technologies has not always been accompanied by a corresponding understanding of their effects on human health and ecosystems. Here, we compare toxicological effects of pristine TiO2, ZnO and SiO2, and coated SiO2 nanoparticles and evaluate their suitability as additives to consolidants of weathered construction materials. First, WST-1 and LDH assays were used to determine the viability of human alveolar A549 cells at various nanoparticle concentrations (0–250 μg mL−1). While the pristine TiO2 and coated SiO2 nanoparticles did not exhibit any cytotoxic effect up to the highest tested concentration, the pristine SiO2 and ZnO nanoparticles significantly reduced cell viability. Second, as all the developed nanoparticle-modified consolidants increased the mechanical strength of weathered sandstone, the decisive criterion for the selection of the most suitable nanoparticle additive was as low toxicity as possible. We believe that this approach will be of high importance for industry to identify materials representing top functional properties and low toxicity at an early stage of the product development.