This study aimed to investigate the effects of supplementation with bacterial cellulose (BC), konjac glucomannan (KGM) and combined BC/KGM fiber on high-fat (HF)-diet-induced obesity in C57BL/6J mice. The results showed that combined supplementation with BC/KGM in HF-fed mice was more efficient in reducing body weight, lowing serum lipid profiles and suppressing insulin resistance than single supplementation with BC or KGM. Moreover, supplementation with combined BC/KGM fiber more efficiently alleviated HF-diet-induced liver injury by decreasing hepatic steatosis in comparison with supplementation with BC or KGM alone. Furthermore, supplementation with combined BC/KGM fiber in HF-fed mice had a more positive effect on obesity-associated hepatic inflammation by reducing levels of TNF-α and IL-6 and suppressing the protein expression of Nrf-2/ARE in comparison with supplementation with BC or KGM alone. Consumption of these dietary fibers, especially mixed BC/KGM, resulted in an improved antioxidant defense system and reduced lipid peroxidation in the liver by increasing the activity of antioxidant enzymes and reducing the formation of MDA in the liver. Moreover, supplementation with these fibers regulated the levels of leptin and adiponectin and inhibited the protein expression of PPARγ by reducing the size of cells in the adipose tissue of HF diet-fed mice. Therefore, fiber supplementation (especially with combined BC/KGM) efficiently inhibited HF-induced obesity in mice by reducing insulin resistance, liver injury and inflammation, enhancing the antioxidant defense system and regulating the secretion of adipocytokines and adipogenesis-associated proteins.