The combination of metal nanoparticles (Pd or Pt NPs) with NAD-dependent thermostable alcohol dehydrogenase (TADH) resulted in the one-flask catalytic double reduction of 3-methyl-2-cyclohexenone to 3-(1S,3S)-methylcyclohexanol. In this article some assumptions about the interactions between a chemocatalyst and a biocatalyst have been proposed. It was demonstrated that the size of the NPs was the critical parameter for the mutual inhibition: the bigger the NPs the more harmful for the enzyme they were even if the NPs themselves were only moderately inactivated. Conversely the smaller the NPs the more minimal the TADH denaturation although they were dramatically inhibited. Resuming the chemocatalysts were very sensitive to deactivation which was not related to the amount of enzyme used while the inhibition of the biocatalyst can be strongly reduced by minimizing the NPs/TADH ratio used to catalyze the reaction. Among some methods to avoid direct binding of NPs with TADH we found that using large Pd NPs and protecting their surfaces with a silica shell the overall yield of 3-(1S,3S)-methylcyclohexanol was maximized (36%).