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Hydroxyapatite (HAp) has been the main protagonist in the quest for an ideal biomaterial for regenerative medicine over the last half a century. To control its properties, this material has commonly been doped with chemical elements other than its natural stoichiometric constituents: Ca, O, P, and H. Here, we report on the first analysis of the biological response to germanium-doped hydroxyapatite (Ge-HAp). Cytotoxicity, osteogenic differentiation induction, and colony formation potential were measured on dental pulp stem cells, while the antimicrobial effect was assessed against Gram-negative Escherichia coli , Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans. All analyses were run in comparison to Ge-free HAp. Cell viability was inversely dependent on the nanoparticle concentration and incubation time. Adding Ge to HAp reduced cell viability relative to HAp after 24–72 h incubation periods, but the effect was reversed after longer incubations, when the viability of cells treated with low doses of Ge-HAp exceeded that of HAp-treated cells and became comparable with control culture. Both HAp and Ge-HAp induced mineral formation in the cell culture, but the effect was more pronounced for Ge-HAp. Likewise, relative to both control cells and cells exposed to HAp, Ge-HAp upregulated the expression of all three osteogenic markers analyzed, namely, alkaline phosphatase, RUNX2, and osteocalcin, exerting the key influence on osteogenesis in its early, differentiation stage. The colony formation capacity of stem cells, however, was impaired by HAp and even more so by Ge-HAp. The antimicrobial effect was dependent on the microorganisms tested. Thus, whereas the antimicrobial activity was absent against E. coli , it was evident against MRSA and C. albicans. While the antibacterial activity against MRSA was weakened by the addition of Ge to HAp, the antimycotic activity against C. albicans was intensified with the addition of Ge. These findings demonstrate a significant potential of Ge-doped HAp nanoparticles in regenerative medicine due to their pronounced biocompatibility, osteoinductivity, and antimicrobial activity. [ABSTRACT FROM AUTHOR]