Zinc oxide nanoparticles were synthesized by co-precipitation method followed by covering with MS (M = Zn, Cd, or Pb) to obtain ZnO/MS core/shell nanoparticles using chemical method. The formation of core/shell nanoparticles were authenticated by various spectroscopic techniques. The photocatalytic activity of the synthesized core/shell nanoparticles shows the significant role of the shell layer in the photodegradation of methylene blue. The antimicrobial activity has been evaluated against two Gram (–ve) (E. coli and K. pneumoniae) and two Gram (+ve) (E. faecalis and S. aureus) bacterial, and two fungi (A. niger and C. albicans) strains. In vitro anti-proliferative activity of ZnO and ZnO/MS core/shell nanoparticles at a concentration of 0.06 M was evaluated against two human cancerous cell lines such as breast (MCF-7) and lung (A549), and one normal human kidney (HEK-293) cell line by MTT assay. DNA fragmentation analysis proved the inhibition of proliferation through induction of apoptosis.