In this investigation, we fabricated biogenic silica-metal phosphate nanocomposites (BSMPNs) using rice husk from agricultural waste as a silica source. The morphologies and dimensions of the synthesized nanocomposites were analyzed using transmission electron microscopy (TEM). Fourier-transform infrared spectroscopy results confirmed that metal phosphate crystals were formed with the biogenic silica. The X-ray diffraction patterns of the BSMPNs showed the presence of hexagonal calcium and iron phosphate and orthorhombic zinc phosphate nanoparticles embedded in the matrix of biogenic silica. The TEM images suggested that spherical and irregularly shaped tiny particles with dimensions between 50 and 100 nm were dispersed in the biogenic silica. The in vitro biological properties of the nanocomposites were studied by a cell viability assay and through the analysis of microscopy images. The cytocompatibility studies proved that the material was nontoxic and had excellent biocompatibility with human mesenchymal stem cells. The synthetic route for these nanocomposites is interesting and may be helpful in the fabrication of various novel silica-based composites and in the exploitation of eco-friendly agricultural biomass. Our results revealed that these nanocomposites can be used in bone tissue engineering.