Integrating the glycerol oxidation reaction (GOR) into aqueous electrochemical systems, such as fuel cells and electrolyzers, offers a promising strategy for utilizing the oxidized energy of glycerol to generate electricity and valuable chemicals. However, challenges remain in optimizing GOR selectivity, reducing electrolysis energy consumption, and enhancing fuel cell voltage and energy density. Recent advancements in GOR electrocatalysis have demonstrated its potential to efficiently convert glycerol into valuable products or electrical energy, even achieving dual functionality in some cases. Additionally, the integration of hybrid dual-electrolyte systems, where a pH gradient is established with a higher pH at the anode than at the cathode, has been shown to significantly improve the performance of GOR-based aqueous devices by harnessing electrochemical neutralization energy (ENE) and creating optimal reaction conditions for both the anode and cathode. In this perspective, we provide a comprehensive exploration of electrochemical GOR and its integration into hybrid dual-electrolyte systems. Given the strong correlation between various factors and GOR performance in hybrid systems, we first provide a brief overview of GOR reaction pathways, catalytic mechanisms, and key performance determinants (including potential, current density, electrolyte selection, and electrocatalyst design) to deepen understanding of fundamental processes and guide catalyst design. We then highlight the integration of GOR into aqueous advanced hybrid dual-electrolyte devices, emphasizing recent breakthroughs and issues warranting further research. Finally, we discuss the current challenges and future prospect concentrating on optimizing hybrid dual-electrolyte systems for large-scale application. This perspective aims to deepen fundamental understanding of GOR application in hybrid dual-electrolyte systems, stimulate scientific curiosity, and guide future research in this emerging field.