Benchtop NMR is becoming an increasingly important tool, sometimes providing a simple and low-cost alternative to high-field NMR. The Achilles heel of NMR and even more critically of benchtop NMR is its limited sensitivity. However, when combined with hyperpolarization techniques, the sensitivity boost can provide excellent sensitivity that can even make benchtop NMR compatible with affinity studies for drug discovery. Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) provides a route to enhancing 13C nuclear magnetic resonance (NMR) sensitivity by more than 5 orders of magnitude for a wide range of small molecules on a benchtop NMR system. We show here how ligands can be secondarily labeled with 13C tags and hyperpolarized with conventional dDNP methods. These hyperpolarized ligands display long nuclear spin-lattice relaxation time constants and can therefore be used to probe interactions with target proteins in conventional dDNP settings. The boost in sensitivity combined with the simplicity of the 13C spectra (one peak per ligand) enables detection on an 80 MHz benchtop NMR spectrometer at micromolar concentrations, which may ultimately provide a way of improving and accelerating the discovery of new drug candidates.