Plant-wide scheduling optimization of multi-grade PET production is of great significance for increasing the economic benefits and market competitiveness of PET plants. However, dealing with changeover operations between the production of products with different grades is challenging due to multiple timing limitations in the actual process. This study proposes a novel plant-wide scheduling optimization model for multi-grade PET production. The model focuses on three major categories of products, namely PET fibers, PET chips, and bottle-grade PET. Considering the impacts of nights and weekends on the production, a hybrid discrete/continuous-time representation method is developed to handle changeover operations with time window constraints. Afterward, a multi-objective optimization framework for multi-grade PET production is formulated to balance economic benefits and production stability. Case studies on a real-world PET plant are presented to verify the effectiveness and applicability of the proposed method.