Cisplatin (CP) has been widely used as an anticancer drug for more than 30 years despite severe side effects due to its low bioavailability and poor specificity. For this reason, it is paramount to study and design novel nanomaterials to be used as vectors capable to effectively deliver the drug to the biological target. The CP square‐planar geometry, together with its low water solubility, suggests that it could be possibly easily adsorbed on 2D graphene nanostructures through the interaction with the related highly conjugated π‐electron system. In this work, pyrene has been first selected as the minimum approximation to the graphene plane, which allows to properly study the noncovalent interactions determining the CP adsorption. In particular, electronic structure calculations at the MP2C and DFT‐SAPT levels of theory have allowed to obtain benchmark interaction energies for some limiting configurations of the CP–pyrene complex, as well as to assess the role of the different contributions to the total interaction: it has been found that the parallel configurations of the aggregate are mainly stabilized around the minimum region by dispersion, in a similar way as for complexes bonded through π‐π interactions. Then, the benchmark interaction energies have been used to test corresponding estimations obtained within the less expensive DFT to validate an optimal exchange‐correlation functional which includes corrections to take properly into account for the dispersion contribution. Reliable DFT interaction energies have been therefore obtained for CP adsorbed on graphene prototypes of increasing size, ranging from coronene, ovalene, and up to C150H30. Finally, DFT geometry optimizations and frequency calculations have also allowed a reliable estimation of the adsorption enthalpy of CP on graphene, which is found particularly favorable (about −20 kcal/mol at 298 K and 1 bar) being twice that estimated for the corresponding benzene adsorption. © 2017 Wiley Periodicals, Inc.