Palladium nanoparticles (Pd NPs) of different shapes and sizes have been synthesized by reducing potassium tetrachloropalladinate(II) by l-ascorbic acid (AA) in an aqueous solution phase in the presence of an amphiphilic nonionic surfactant poly ethylene glycol (PEG) via a sonochemical method. Materials have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray soectrscopy (EDX), Fourier transform infrared (FTIR), surface-enhanced Raman spectroscopy (SERS), particle distribution, and zeta potential studies. Truncated octahedron/fivefold twinned pentagonal rods are formed at room temperature (RT) (25 °C) while hexagonal/trigonal plates are formed at 65 °C. XRD results show evolution of anisotropically grown, phase-pure, and well crystalline face-centered cubic Pd NPs at both temperatures. FTIR and SERS studies revealed adsorption of ascorbic acid (AA) and PEG at NP's surface. Particle's size distribution graph indicates formation of particles having wide size distribution while the zeta potential particle surface is negatively charged and stable. The truncated octahedron/fivefold twinned pentagonal rod-shaped Pd NPs, formed at RT, while thermally stable and kinetically controlled hexagonal/trigonal plate-like Pd NPs, evolved at higher temperature 65 °C. The obtained Pd NPs have a high surface area and narrow pore size distribution. To predict protein reactivity of the Pd cluster, docking has been done with DNA and lung cancer-effective proteins. The cytotoxicity of the Pd NPs has been screened on human lung cancer cells A-549 at 37 °C. The biological adaptability exhibited by Pd NPs has opened a pathway in biochemical applications.