The aim of the present study was to investigate a green and continuous ultrasonic devulcanization process that could be carried out in a short time adjusting the process variables in order to optimize specific required conditions. Ultrasonic assisted devulcanization in a twin-screw extruder was studied and modeled using a face-centered central composite design and desirability functions. Several responses on the D-GTR and on R-GTR were chosen as responses and reduced regression models were obtained by regression analysis.The properties of the D-GTR and R-GTR were influenced by all the process variables as well as interaction effects between them. However, the US was found to be the most influencing process variable for the described screw configuration. Different behaviors were observed for the various responses. For this reason, an optimization was performed in order to maximize the TS and M100, considered the most important parameters for reuse of D-GTR. A relatively low value of US was required to reduce the network density without introducing an excessive degradation of the tire rubber. This study has an important outcome since the approach presented here can be applied to the devulcanization of any type of GTR in order to reach the optimal desirable properties for different applications.