Seventeen adamantane derivatives were synthesized according to facile condensation reaction protocols. Spectral analysis (1H NMR and 13C NMR) was applied to confirm the chemical structure of the obtained substances. The synthesized compounds were tested for in vitro antimicrobial activity against a panel of Gram-positive and Gram-negative bacterial strains and towards fungi from Candida spp. Among them, four derivatives numbered 9, 14, 15 and 19 showed the highest antibacterial potential with MIC = 62.5–1000 µg/mL with respect to all Gram-positive bacteria. S. epidermidis ATCC 12228 was the most susceptible among the tested bacterial strains and C. albicans ATCC 10231 among fungi. Additionally, the cytotoxicity for three derivatives was measured with the use of the MTT test on A549, T47D, L929 and HeLa cell lines. Our cytotoxicity studies confirmed that the tested substances did not cause statistically significant changes in cell proliferation within the range of the tested doses. Keywords: adamantane derivatives; Schiff bases; hydrazide–hydrazone; biological activity; cytotoxicity; antimicrobial activity; antibacterial activity; antifungal activity