The manuscript portrays environmentally benign and cost-effective biogenic synthesis of Zinc sulfide nanoparticles (ZnS NPs) using Calendula officinalis flower extract (CFE). X-ray diffractogram of Calendula officinalis flower extract-mediated ZnS NPs [ZnS@CFE NPs] showed a cubic crystal configuration with \(\:F\bar{4}3m\) space group as confirmed using the Rietveld refinement method. The average crystallite size of ZnS@CFE NPs was found to be 16 nm. The absorption spectrum of ZnS@CFE NPs showed a characteristic peak at 312 nm with a band gap energy (\({E}_{g}\)) of 3.81 eV. The broad peak at 3204 cm− 1 in the FTIR spectrum was characteristic of various hydroxyl groups, such as alcohol and phenol, belonging to CFE, and the peak at 533 cm− 1 was attributed to Zn-S bending, thereby confirming the formation of ZnS NPs. Biosynthesized ZnS@CFE NPs possessed a uniform and homogeneous granular microstructure with an average grain size of 19 ± 0.98 nm. The antibacterial activity of biosynthesized ZnS@CFE NPs was evaluated using the disk diffusion assay, demonstrating dose-dependent inhibition against P. aeruginosa, S. typhi, S. aureus, and L. monocytogenes, with the strongest effect observed at 100 µg/mL. CFE@ZnS NPs showed an efficiency of 59.96% against P. aeruginosa at 100 µg/mL. The antibacterial mechanism involves reactive oxygen species (ROS) generation, membrane disruption, Zn2+ ion release, and DNA damage, highlighting ZnS@CFE NPs as a promising antimicrobial agent.
