BACKGROUND AND AIM: Prediabetes is an unavoidable process and a high risk factor for developing of type 2 diabetes. Tangningtongluo (TNTL) tablet is a kind of pure plant preparation in hospital and used for the diabetes (, xiāo kě bìng) caused by deficiency of both Qi and Yin (，qì yīn liǎng xū). However, the effect of TNTL tablet on prediabetes has not been reported for now. This study was aimed to investigate the effect and related mechanism of TNTL tablet on prediabetes. EXPERIMENTAL PROCEDURE: Prediabetic mice induced by a high-sugar and high-fat diet combined with streptozotocin were treated with TNTL tablet, and the pharmacodynamics and related mechanism were studied. RESULTS AND CONCLUSION: Our results showed that TNTL tablet reduced body weight and regulated the disorder of glucose and lipid metabolism in prediabetic mice. The function and the pathological changes of liver and islet tissue were improved after TNTL tablet treated prediabetic mice. Additionally, TNTL tablet decreased the levels of MDA, TNF-α, IL-1β and IL-6 in serum, increased the contents of SOD and GSH-px, up-regulated the expression of p-PI3K and p-AKT protein, and down-regulated the expression of p-IKK and p-NF-κB p65 protein in liver tissue. This study revealed that TNTL tablet could improve insulin sensitivity and insulin resistance in prediabetic mice, and delay the procession of prediabetes to diabetes, which might be related to inhibiting IKK/NF-κB signaling pathway, exerting anti-inflammatory and antioxidant effects, and activating PI3K/AKT signaling pathway.