Toxic inhibitory compounds from lignocellulose pretreatment are the major obstacle to achieve high bioconversion efficiency in biorefinery fermentations. This study shows a unique glucose oxidation catalysis of Gluconobacter oxydans with its gluconic acid productivity free of inhibitor disturbance. The microbial experimentations and the transcriptome analysis revealed that both the activity of the membrane-bound glucose dehydrogenase and the transcription level of the genes in periplasmic glucose oxidation respiratory chain of G. oxydans were essentially not affected in the presence of inhibitory compounds. G. oxydans also rapidly converted furan and phenolic aldehyde inhibitors into the less toxic alcohols or acids. The synergy of the robust periplasmic glucose oxidation and the rapid inhibitor conversion of G. oxydans significantly elevated the efficiency of the oxidative fermentation in lignocellulose hydrolysate. The corresponding genes responsible for the conversion of furan and phenolic aldehyde inhibitors were also mined by DNA microarrays. The synergistic mechanism of G. oxydans provided an important option of metabolic modification for enhancing inhibitor tolerance of general fermentation strains.