Development of scaffolds from naturally available biomaterials for bone tissue engineering is an interesting research area. Among the different scaffolds established for this purpose, biogenic silica nanostructure (BSN) serves as a promising naturally available inorganic and biocompatible material. A few studies have demonstrated the intrinsic biological activity of synthetic silica nanoparticles. The virtually infinite promising applications of these structures rely on their erratic physicochemical properties. We have derived BSNs from Sorghum bicolor seed head using a progressive approach. The intrinsic biological activities were analyzed using human mesenchymal stem cells (hMSCs) as an in vitro model with MTT assay and acridine orange/ethidium bromide staining. We also studied the role of BSNs in the osteogenic differentiation of hMSCs using alkaline phosphatase staining, alizarin red staining, and gene expression analysis. BSNs increased the formation of calcium nodules and stimulated alkaline phosphatase (ALP) activity. Significant changes and/or upregulation in the expression of osteogenic prominent markers such as ALP, bone morphogenetic protein-2 (BMP-2), BMP-4, bone sialoprotein (BSP), collagen-1 (Col-1), and Runt-related transcription factor 2 (RUNX2) genes were observed. Taken together, these results suggest that BSNs exhibited biocompatibility and induced osteogenic differentiation of hMSCs, indicative of their potential applications for bone tissue engineering.