Dragmacidin D, an emerging biologically active marine natural product, has attracted attention as a lead compound for treating Parkinson's and Alzheimer's diseases. Prominent structural features of this compound are the two indole pyrazinone bonds and the presence of a polar aminoimidazole unit. We have established a concise total synthesis of dragmacidin D using direct C H coupling reactions. Methodological developments include (i) Pd-catalyzed thiophene indole C-H/C-I coupling, (ii) Pd-catalyzed indole pyrazine N-oxide C-H/C-H coupling, and (iii) acid-catalyzed indole pyrazinone C-H/C-H coupling. These regioselective catalytic C-H couplings enabled us to rapidly assemble simple building blocks to construct the core structure of dragnnacidin D in a step-economical fashion.