First time in this study, the antibacterial effects of Axinyssa digitata sponge extracts and Axinyssa digitata-based cupper hybrid nanoflowers (Cu hNFs) were evaluated. Herein, hybrid nanoflowers (Cu hNFs) were produced by combining Axinyssa digitata sponge extract with Cu2+ ions in Phosphate-buffered saline (PBS) (at pH 7.4) at room temperature for three days using green synthesis method. The shape and size of hNFs were evaluated using scanning electron microscope (SEM) images. Energy dispersive X-ray spectroscopy (EDX) mapping was used to determine the presence of Cu metals and other components. X-ray diffraction (XRD) is a non-destructive analysis method that was used to determine of the crystallographic properties of materials and the phases they contain. Fourier-transform infrared spectroscopy (FT-IR) peaks were used to discuss the presence of functional groups that played a key role in the synthesis. The Cu-hNFs had antimicrobial activity against selected microorganisms. This research is expected to provide knowledge on hNFs synthesis and antimicrobial activity application investigations using Axinyssa digitata rather than biomolecules obtained through costly and time-consuming methods.