Prediabetes is a transitional state between normal blood glucose levels and diabetes, but it is also a reversible process. At the same time, as one of the most important tissues in the human body, the metabolic disorder of skeletal muscle is closely related to prediabetes. Huidouba (HDB) is a clinically proven traditional Chinese medicine with significant effects in regulating disorders of glucose and lipid metabolism. Our study aimed to investigate the efficacy and mechanism of HDB in prediabetic model mice from the perspective of skeletal muscle. C57BL/6J mice (6 weeks old) were fed a high-fat diet (HFD) for 12 weeks to replicate the prediabetic model. Three concentrations of HDB were treated with metformin as a positive control. After administration, fasting blood glucose was measured as an indicator of glucose metabolism, as well as lipid metabolism indicators such as total triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), free fatty acid (FFA), and lactate dehydrogenase (LDH). Muscle fat accumulation and glycogen accumulation were observed. The protein expression levels of p-AMPK, AMPK, PGC-1α, PPAR-α, and GLUT-4 were detected. After HDB treatment, fasting blood glucose was significantly improved, and TG, LDL-C, FFA, and LDH in serum and lipid accumulation in muscle tissue were significantly reduced. In addition, HDB significantly upregulated the expression levels of p-AMPK/AMPK, PGC-1α, PPAR-α, and GLUT-4 in muscle tissue. In conclusion, HDB can alleviate the symptoms of prediabetic model mice by promoting the AMPK/PGC-1α/PPARα pathway and upregulating the expression of GLUT-4 protein.