Introduction: Mitochondria play a key role in maintaining the homeostasis of cell metabolism. Mitochondrial dysfunction and oxidative phosphorylation disorders play an important role in the pathogenesis of diabetic skeletal muscle. In this regard, the aim of this study is to investigate the effect of type 2 diabetes on skeletal muscle mitochondrial markers and the use of Hippophae rhamnoides extract with metformin as a complementary medicine. Methods: 30 C57BL/6 mice with 6-7 week-olds were divided into five groups: control group, Type 2 diabetes group, 3. The group with type 2 diabetes was treated with metformin, Type 2 diabetes group treated with Hippophae rhamnoides extract, Type 2 diabetes group treated with metformin and Hippophae rhamnoides extract. The genes obtained from bioinformatics analysis. To investigation gene expression, the Real-Time PCR technique was used, and muscle ATP concentration was assesd using the ELISA method. Findings: In the diabetes group, compared to the control group, the expression of mt-Nd5/PGC1α/ATP5/mt-Nd1 genes and ATP concentration decreased (p<0.001). Consumption of Hippophae rhamnoides extract and metformin separately increased the expression level of mt-Nd5/PGC1α/ATP5/mt-Nd1 genes and ATP concentration (p<0.001). Simultaneous consumption of Hippophae rhamnoides extract and metformin significantly increased the expression of mt-Nd5/PGC1α/ATP5/mt-Nd1 genes and ATP concentration (p<0.001). Conclusion: Hippophae rhamnoides extract and metformin can regulate mt-Nd5/PGC1α/ATP5/mt-Nd1 network and ATP concentration in muscle tissue.