Half sandwich ruthenium, rhodium and iridium complexes containing pyridyl chalcone analogues (L1 and L2) are prepared by the reaction of [(arene)M(µ-Cl)Cl]2 (arene = benzene, p-cymene, Cp*) and (M = Ru, Rh/Ir)] with L1 and L2 in 1:2 (M:L) ratio. Eight neutral mononuclear complexes (1–8) were obtained and characterized using FT-IR, 1H NMR, 13C NMR, ESI mass and UV–Vis spectroscopic methods. The molecular structures of complexes 2, 4, 5 and 7 are established by single crystal X-ray diffraction studies. Antibacterial studies were tested against three strains of bacterial microorganisms Staphylococcus aureus (gram +ve), Klebsiella pneumoniae (gram −ve) and Escherichia coli (gram −ve). Further the cytotoxicity study of the pyridyl chalcone derivatives and their complexes were evaluated against the human colorectal cancer cell lines HT-29, HCT-116 p53+/+, HCT-116 p53−/− and ARPE-19 (non-cancer retinal epithelium).