The effects of high hydrostatic pressure treatment (100 to 600 MPa) coupled with heat treatment (0 to 60 °C) on the inactivation of peroxidase (POD) and polyphenoloxidase (PPO) in red grapes (Vitus viniferd) have been studied. The examination of the complex interactions between pressure and temperature has been carried out using a central composite rotatable design (CCRD). The response surfaces show that the lowest activity of POD (55.75%) and PPO (41.86%) was found to be at 60 °C at 600 MPa and 100 MPa, respectively.