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Cuttlefish bones are an inexpensive source of calcium carbonate, which are produced in large amounts by the marine food industry, leading to environmental contamination and waste. The nontoxicity, worldwide availability and low production cost of cuttlefish bone products makes them an excellent calcium carbonate precursor for the fabrication of hydroxyapatite. In the present study, a novel oil-bath-mediated precipitation method was introduced for the synthesis of hydroxyapatite (Hap) nanorods using cuttlefish bone powder as a precursor (CB-Hap NRs). The obtained CB-Hap NRs were investigated using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA) techniques to evaluate their physicochemical properties. The crystallite size (20.86 nm) obtained from XRD data and the elemental analysis (Ca/P molar ratio was estimated to be 1.6) showed that the Hap NRs are similar to that of natural human bone (≈1.67). Moreover, the FTIR data confirmed the presence of phosphate as a functional group and the TGA data revealed the thermal stability of Hap NRs. In addition, the antibacterial study showed a significant inhibitory effect of CB-Hap NRs against S. aureus (zone of inhibition – 14.5 ± 0.5 mm) and E. coli (13 ± 0.5 mm), whereas the blood compatibility test showed that the CB-Hap NRs exhibited a concentration-mediated hemolytic effect. These biogenic CB-Hap NRs with improved physicochemical properties, blood compatibility and antibacterial efficacy could be highly beneficial for orthopedic applications in the future.