We report a Ruthenium (Ru)-catalyzed cocktail labeling strategy that offers high catalytic efficiency and deeper proteome coverage through a straightforward “mix and lighten” workflow. Our approach uses a highly efficient transition metal complex (TMC)-based catalyst, along with two compatible biotin probes for biased substrates. Our results highlight the potential roles of many previously underestimated CSPs. We provide solid and detailed evidence supporting the efficacy of our method, demonstrating the advantages and uniqueness of Ru-based proximity labeling. This 'cocktail labeling' concept mitigates biases from different labeling methods, broadening substrate scopes and potentially inspiring advancements in other proximity labeling methods.