Biological methods have been used to synthesize silver nanoparticles through materials such as bacteria, fungi, plants, and propolis due to their reducing properties, stabilizer role and environmentally friendly characteristic. Considering the antimicrobial activity of propolis as well as the broad‐spectrum antibacterial effects of silver nanoparticles, this study aim to describe the use of Brazilian propolis to synthesize silver nanoparticles (AgNP‐P) and investigate its antimicrobial activity. The synthesis was optimized by factorial design, choosing the best conditions for smaller size particles. AgNP‐P demonstrated a maximum absorbance at 412 nm in ultraviolet‐visible spectra, which indicated a spherical format and its formation. Dynamic light scattering demonstrated a hydrodynamic size of 109 nm and polydispersity index less than 0.3, showing a good size distribution and stability. After its purification via centrifugation, microscopy analysis corroborates the format and showed the presence of propolis around silver nanoparticle. X‐ray diffraction peaks were attributed to the main planes of the metallic silver crystalline structure; meanwhile infrared spectroscopy demonstrated the main groups responsible for silver reduction, represented by ∼22% of AgNP‐P indicates by thermal analysis. Our product revealed an important antimicrobial activity indicating a synergism between propolis and silver nanoparticles as expected and promising to be an effective antimicrobial product to be used in infections.