<p>Wet chemical combination of <i>Hibiscus rosa-sinensis</i> flower extract and selenous acid (H₂SeO₃) resulted in biogenic Selenium(0) nanoparticles. The chemical bottom-up approach was used to produce piperine-loaded flavonoid surface-capped Selenium(0) nanoconjugates. These Selenium(0) nanoparticles and piperine-loaded nanoconjugates were characterized using ultraviolet–visible absorption studies, Fourier-transform infrared spectroscopy, and photoluminescence emission spectroscopic techniques to confirm the formation of nanoparticles. The crystallite sizes, packing, and morphologies of Selenium(0) and piperine-loaded Selenium(0) nanoconjugates were determined from X-ray diffraction (XRD) patterns and transmission electron microscopy analysis. The XRD analysis had exhibited the amorphous nature of nanoconjugates with mean size 56&#xa0;nm. After confirmation of physiochemical properties of piperine-loaded Selenium(0) nanoconjugates, primary in vitro synergistic biocompatibility was studied and compared with free drug piperine over <i>E. coli</i> and <i>Staphylococcus aureus.</i> The neuroprotective effects of nanoconjugates were estimated by in vitro MTT assay and eosin dye staining images of Parkinson neural cell lines with SH-SY5Y model. These nanoconjugates had exhibited synergisti<i>c</i> antimicrobial and neuroprotective effects to repair of neuron peroxide damaged cells from cell viability on Parkinson model cells with good biomedical potential.</p> Graphical abstract <p></p>