We report the development and implementation of hybrid methods that combine quantum mechanics (QM) with molecular mechanics (MM) to theoretically characterize thiolated gold clusters. We use, as training systems, structures such as Au-25(SCH2-R)(18) and Au-38(SCH2-R)(24), which can be readily compared with recent crystallographic data. We envision that such an approach will lead to an accurate description of key structural and electronic signatures at a fraction of the cost of a full quantum chemical treatment. As an example, we demonstrate that calculations of the H-1 and C-13 NMR shielding constants with our proposed QM/MM model maintain the qualitative features of a full DFT calculation, with an order-of-magnitude increase in computational efficiency.