C-H bond activation reactions facilitate highly efficient molecular transformations without requiring pre-activating substrates. While the majority of reported reaction systems for C-H activation rely on metal complexes, certain reactions have demonstrated unique or superior catalysis of metal nanoparticles. This Concept article seeks to delineate recent reports that examine the novel catalysis and design strategy of supported metal nanoparticles for C-H bond activation reactions. These reactions include oxidative homocoupling of arenes, dehydrogenative alkylation of benzenes, selective H/D exchange reactions, and α,β-dehydrogenation of ketones.