Bio-apatite based materials were prepared from bovine bone wastes (BBW) by thermal treatments using a direct flame (BBS) and annealing at 500–1,100 °C (BB500–BB1100). These low-crystalline materials were characterized by means of SEM, XRD, FTIR, TG, and pHPZC and were used for the adsorption of Hg(II) ions. A CCD-RSM design was used to optimize and analyze independent variables consisting of initial mercury concentration (10–100 mg L−1), pH (2–9), adsorbent mass (0.1–0.5 g), temperature (20–60 °C), and contact time (15–120 min). The results indicated that the order of the mercury uptakes for bio-apatite based adsorbents was BB500 > BB600 > BB800 > BB1100 > BBS > BBW. The dissolution–precipitation and ion-exchange reaction are the two dominant mechanisms for the removal of Hg(II) ions at low and high pH values, respectively. The CCD-RSM predicted maximum mercury adsorption of 99.99% under the optimal conditions of 51.31 mg L−1, 0.44 g, 6.5, 67.5 min, and 50 °C for initial mercury concentration, adsorbent mass, pH, contact time, and temperature, respectively. The findings of the present study revealed that the bio-apatite based materials, particularly BB500, are suitable and versatile adsorbents for the treatment of mercury-containing wastewater.