Valorization of wastes and by-products using environmentally friendly technologies with an optimal cost–benefit relationship is a current major issue in agri-food industries. An original tool was recently developed for multi-criteria optimization of an ultrasound-assisted extraction (UAE) process including the assessment of environmental impacts using Life Cycle Assessment. In the present work, this methodology was adapted and applied to another green extraction process, microwave-assisted extraction (MAE), with the same case study, valorization of antioxidant polyphenols from downgraded beet seeds. Once built, the obtained multi-criteria optimization tool was used to investigate performances of the MAE process regarding productivity criteria (polyphenol concentration and antioxidant activity of the extracts), energy consumption and environmental impacts as functions of operating parameters (time, solvent composition, microwave power density, and liquid–solid ratio). The MAE process was optimized under different constraints and compared to the UAE process. For the studied conditions and different investigated scenarios, MAE enabled obtaining extracts with higher polyphenol concentrations and antioxidant activity (approximately 33% and 23% enhancements, respectively), and to strongly reduce extraction duration (by a factor up to 6), whereas UAE enabled reducing the energy consumption (up to 3.6 fold) and the environmental impacts (up to 12% for climate change).