Rare Earth elements in the lanthanide series are regarded as one of the finest options for the cationic substitution of calcium ions in hydroxyapatite (HA) because of their favorable impact on the biological characteristics of substituted HA. Neodymium and cerium were used to substitute 5% of calcium ions in HA, prepared via the wet precipitation method. Characterization tests for pure and substituted HA were conducted using XRD, FTIR, EDS, and FESEM. The results showed that changing part from calcium ions in hydroxyapatite to Nd and Ce ions altered its structure, composition, and morphology. Regarding the biological tests, the cytotoxicity test revealed a change in IC50 for both normal and cancer cell lines, where substitution part of the Ca ions with rare Earth elements led to increasing antitumor activity in comparison with HA without substitution; in addition, antibacterial and fungicide activity was evident for both HA and Nd-Ce/HA, with a modest increase in antibacterial activity of Nd-Ce/HA against S. epidermidis and E. coli in comparison with HA. These findings may shed light on the process by which Nd and Ce ions improve the biological characteristics of pure HA and the increased potential of these bioceramics.