High-pressure homogenization (HPH) process is a nonthermal, nonconventional, emerging technology for the continuous processing of fluid materials. It has been studied as an alternative processing for the preservation of fruit and vegetable juices. Inactivation of endogenous enzymes in juices is an important concern for food processing, aiming to guarantee juice stability and sensory acceptance during product shelf life. However, HPH can physically change the enzyme configuration, leading to activation, inactivation, and/or stabilization, depending on the processing parameters, enzyme, and food matrix. These different results expand the possibilities for food processing. This chapter describes the principles of HPH technology, the mechanisms involved in enzyme activation, inactivation, and stabilization, and the main effects on juice quality parameters, rheology, and phytochemical profile. To conclude, final remarks and future challenges of HPH application to modify enzyme activity were described.