It has been well established that hepatic insulin signaling is significantly affected by the antioxidative status of the liver. In this study, we first confirmed that skate skin collagen peptide (SSCP) administration has dose-dependent positive effects on the change in the glucose level as evidenced by oral glucose tolerance tests. Therefore, the beneficial effects of SSCP-showing antioxidative and anti-inflammatory activities-on insulin resistance were examined in high-fat diet (HFD)-fed mice. C57BL/6J mice orally received SSCP at doses of 100, 200, and 300 mg per kg bw per day along with a HFD for 8 weeks (n = 9 per group). Water was given to the HFD- or chow diet-only group as a vehicle. Compared with the HFD group, the final body weight was reduced in all the SSCP-treated groups in a dose-dependent manner. The hepatic protein expression levels of the phosphorylated insulin receptor substrate, phosphorylated phosphatidylinositol 3-kinase, and phosphorylated protein kinase B were increased in the SSCP-treated groups, which led to reduced plasma insulin and HOMA-IR levels (P < 0.05). The hepatic protein expression levels of nuclear factor erythroid 2-related factor 2-mediated antioxidant enzymes were increased in the SSCP-treated groups, whereas those of nuclear factor kappa B-regulated inflammatory enzymes and mediators were decreased (P < 0.05). These effects were dose-dependent. It is apparent that SSCP might enhance insulin sensitivity by increasing the antioxidative status and suppressing the inflammatory response in the liver.