Development of biocompatible and high-performance heterogeneous catalysts for bioconjugation and cell labeling is highly challenging. Melanin has previously been used as a target for melanoma imaging and therapy. Herein, this important biomarker was transferred into a novel catalytic platform. A biocompatible Cu(i)/melanin dot-based catalyst [Cu(i)/M-dots] was easily prepared and exhibited high catalytic activity and excellent reusability in various Cu(i)-catalyzed azide-alkyne cycloadditions (CuAAC). Furthermore, DNA bioconjugation was carried out efficiently using Cu(i)/M-dots under ligand-free and reductant-free conditions, and the Cu(i)/M-dots could easily be removed by centrifugation. Lastly, the integrin receptor (alkyne RGD targeted) of U87MG cells was effectively labelled with a fluorescent dye (Cyanine5.5 azide) in combination with Cu(i)/M-dots. These attractive properties of Cu(i)/M-dots render it a promising catalytic platform in bioconjugation and chemical biology applications.