One homoleptic (1) and three heteroleptic (2–4) palladium(II) complexes were synthesized and characterized by various physicochemical techniques, i.e., elemental analysis, FTIR, Raman spectroscopy,1H,13C, and31P NMR. Compound1was also confirmed by single crystal XRD, showing a slightly distorted square planar geometry. The antibacterial results obtained via the agar-well diffusion method for compound1were maximum among the screen compounds. All the compounds have shown good to significant antibacterial results against the tested bacterial strains,Escherichia coli, Klebsiella pneumonia,andStaphylococcus aureus,except2againstKlebsiella pneumonia. Similarly, the molecular docking study of compound3has shown the best affinity with binding energy scores of −8.6569, −6.5716, and −7.6966 kcal/mol againstEscherichia coli, Klebsiella pneumonia,andStaphylococcus aureus, respectively. Compound2has exhibited the highest activity (3.67 µM), followed by compound3(4.57 µM),1(6.94 µM), and4(21.7 µM) against the DU145 human prostate cancer cell line using the sulforhodamine B (SRB) method as compared to cisplatin (>200 µM). The highest docking score was obtained for compounds2(−7.5148 kcal/mol) and3(−7.0343 kcal/mol). Compound2shows that the Cl atom of the compound acts as a chain side acceptor for the DR5 receptor residueAsp B218and the pyridine ring is involved in interaction with theTyr A50residue via arene-H, while Compound3interacts with theAsp B218residue via the Cl atom. The physicochemical parameters determined by the SwissADME webserver revealed that no blood-brain barrier (BBB) permeation is predicted for all four compounds, while gastrointestinal absorption is low for compound1and high for the rest of the compounds (2–4). As concluding remarks based on the obtained in vitro biological results, the evaluated compounds after in vivo studies might be a good choice for future antibiotics and anticancer agents.