<p>Synthetic biology aims to use interchangeable and independent components to develop specialized systems within cellular and cell-free environments to reconfigure natural genetic systems and create innovative tools for biomedicine and industry. Supramolecular nanocatalysts, which use various mechanisms to enhance catalytic reactions, are being explored as components of synthetic gene circuits to optimize metabolic pathways. In this Review, we discuss progress in the incorporation of supramolecular nanocatalysts into cellular systems. We focus on their design, the types of interactions that serve to maintain their supramolecular structure and especially their integration into mammalian cells, as exemplified by actual and potential applications for energy production, energy conversion and novel therapeutics. We also discuss the interactions between supramolecular nanocatalysts and cellular components in metabolic processes and the potential of such combined systems to underpin future breakthroughs in biotechnology and medicine.</p>