Microorganisms create various health issues; semiconductor nanostructures have raised interest because of antimicrobial properties for suppressing microbial growth. Herein, we report the synthesis of ZnSe nanostructures (NSs) using a green coprecipitation method, and the assynthesized samples were annealed at 100, 150, and 200 °C temperatures. The synthesized samples were analyzed for structural, morphological, optical, and antibacterial properties. The growth of nanorods was confirmed by TEM micrographs and that of nanoparticles by FESEM and TEM micrographs. The cubic zinc blender phase of samples was confirmed by XRD. The high-intensity electron−phonon (e−ph) interactions and LO modes were confirmed by the Raman spectra. The UV−visible absorption spectra predicted the blue shift in optical band gaps of ZnSe NSs from their bulk counterparts. The PL spectra and associated CIE diagram indicated that the as-synthesized and annealed NSs produce blue color. The investigated antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus implies the superior biological activity of the as-synthesized and annealed samples at 200 °C. The annealing enhances photoluminescence and antimicrobial activities of ZnSe NSs. The enhanced luminscence properties of ZnSe NSs make them suitable for preparing more efficient blue LEDs and lasers for medical applications. The as-synthesized and annealed ZnSe NSs are found effective against the growth of microorganisms, and sustaining this tendency for 1 week provides a strong basis for the development of new drugs against bacterial infections for supporting the pharmaceutical industry.