The aim of this work was to produce hydroxyapatite powder (HA) containing the dry extract of green and red propolis, and to evaluate the possible bactericidal activity of these materials over a short period of time through a fast release system. The ethanolic extracts of green and red propolis (EEP) were incorporated into the material by spray drying. After release tests, powders containing dry EEP were characterized regarding the content of total phenolics and flavonoids. Material characterization was undertaken by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The antimicrobial activity was evaluated by plate colony counting, minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against Staphylococcus aureus (S. aureus). The cytotoxicity of the materials was determined by the neutral red incorporation method. The materials showed apparently spherical morphology, indicating a decrease in the degree of agglomeration with the addition of propolis. Characteristic HA and propolis functional groups were observed in the FTIR. The materials showed a higher release of phenolics and lower amounts of flavonoids when compared to the EEP, with the higher amounts of flavonoids observed for HA with red propolis. A bactericidal effect was observed for all materials within the interval of 0.5 and 1 h, showing lower inhibitory activity (MIC) and higher bactericidal activity (MBC) when compared to the EEP, with the best results attributed to HA with red propolis. The IC50 values (which is the concentration needed to inhibit cell growth by 50%) obtained from the cytotoxicity assay for HA with the green and red propolis lay between MIC and MCB. Considering these results, it is suggested that HA and propolis may be used as a possible antimicrobial agent, inhibiting the growth of S. aureus, although further in vivo biocompatibility should be investigated before using this material as a medical device with bactericidal potential.