Samarium-doped nanohydroxyapatite is a biomaterial with nerve regeneration activity and bioimaging. In this work, Sm/HAp; (Ca 10−x Sm x (PO 4 ) 6 (OH) 2 ) (0 ≤ x ≤ 1) was synthesized using the hydrothermal method and thermally treated from 200 to 800 °C. The samples were characterized by transmission electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, Raman spectroscopy, and luminescence spectroscopy. The results confirmed the successful integration of Sm 3+ ions into the hydroxyapatite. Our findings revealed the influence of the Sm 3+ content and thermal treatment on the emission properties, obtaining a maximum emission at Sm = 0.05 thermally treated at 800 °C. The SH-SY5Y neuroblastoma cell viability study revealed a Sm 3+ concentration-and particle size-dependent response. This research emphasizes the optical and cell viability of Sm/HAp in SH-SY5Y neuroblastoma cells, making them suitable for further research as agents that activate regenerative processes in cells and neurons.