In this study, a novel, simple, and ecologically safe way to design an Au/ZnO composite was achieved using a polydopamine (PDA) biopolymer as a reductant and encapsulating media. The anchored gold ions were reduced over the PDA-modified ZnO effectively without any harsh reagents. The abundant amino- and hydroxyl-groups over PDA functioned as green reducing agents to cap and reduce Au ions on the ZnO surface. The planned nanocomposites’ effective synthesis was confirmed by field emission-scanning electron microscopy (FE-SEM), energy-dispersive X-ray (EDX), elemental mapping, transmission electron microscopy (TEM), inductively coupled plasma (ICP), and X-ray diffraction (XRD) analysis. Additionally, the ZnO@PDA/Au nanoparticles (NPs) demonstrated potent catalytic activity via Sonogashira coupling in the C-C bond formation mechanism. It is possible to recycle ZnO@PDA/Au after eight consecutive reaction cycles. The synthesis of many stilbene derivatives was accomplished by efficiently coupling phenyl acetylene with aryl halides. The bio-application of the ZnO@PDA/Au nanocomposite for anti-bladder cancer (BC) research against the related cell lines 5637 and TCCSUP was also investigated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In a dose-dependent fashion, the material decreased the cell survival of the malignant breast cell line. The cell lines’ respective IC50 values for the nanocomposite were found to be 208 and 195 μg/mL. ZnO@PDA/Au NPs were used in a 2,2-Diphenyl-1-picrylhydrazyl (DPPH) experiment to assess the antioxidant activity, and the findings revealed an IC50 value of 198 µg/mL. Soon, cancer treatment may appear quite promising given the impressive results demonstrated by the produced nanocomposite.