The stability and exchange interaction mechanism of a doped Zn12O12 cluster with Mn and C atoms were investigated by first-principles calculations. For the Mn-doped Zn12O12 cluster, it is identified that a superexchange interaction deriving the hybridization between the Mn 3d(2/x)-2/y and O 2p(xy) orbitals dominates the Mn(↑)-Mn(↓) antiferromagnetic coupling, although a direct exchange interaction deriving the Mn-Mn bonding is also found. In order to turn the Mn spin state in the Mn-doped Zn12O12 cluster, C doping is undertaken to change the magnetic interactions of these impurities. It is proved that the C incorporation into the Mn-doped Zn12O12 cluster destroys the short-ranged antiferromagnetic coupling, where multiple exchange interactions take over, including the direct exchange interaction and the kinetic p-d exchange interaction partially due to the geometric distortion and surface effect with dangling bonds (sp(2)-like hybrids). It is concluded that the kinetic p-d exchange interaction plays a dominant role in Mn/C-doped Zn12O12 clusters.