Although protein kinase inhibitors present excellent pharmaceutical opportunities, lack of selectivity and associated therapeutic side effects are common. Bisubstrate-based inhibitors targeting both the high-selectivity peptide substrate binding groove and the high-affinity ATP pocket address this. However, they are typically large and polar, hampering cellular uptake. This paper describes a modular development approach for bisubstrate-based kinase inhibitors furnished with cell-penetrating moieties and demonstrates their cellular uptake and intracellular activity against protein kinase C (PKC). This enzyme family is a longstanding pharmaceutical target involved in cancer, immunological disorders, and neurodegenerative diseases. However, selectivity is particularly difficult to achieve because of homology among family members and with several related kinases, making PKC an excellent proving ground for bisubstrate-based inhibitors. Besides the pharmacological potential of the novel cell-penetrating constructs, the modular strategy described here may be used for discovering selective, cell-penetrating kinase inhibitors against any kinase and may increase adoption and therapeutic application of this promising inhibitor class.