Achyranthes aspera is an herb found in the Indian subcontinent and has been used for decades because of its traditional anti-diabetic and antiobesity properties. Since studies are not reported on Achyranthes aspera protection in high-fat diet and diabetes-induced animal models, our aim was to investigate the protective effect of root extract of Achyranthesaspera on the combined effect of high-fat diet and streptozotocin-induced biochem. changes in Wistar rats. To achieve this aim, the objectives of the study were to estimate the body weight, serum glucose, insulin, Glycated Hb(HbA1c), Homeostatic Model Assessment of Insulin Resistance (HOMA- IR), serum lipid profile, and liver glycogen among the Wistar rats which were divided into 6 groups having 6 rats in each group. Group 1 - control rats Group 2 - diabetic group rats, Group 3 - HFD diabetic rats and the rats from groups 4 to 6 were given a high-fat diet+ Streptozotocin 40 mg/kg + a low dose of root extract of Achyranthes aspera (250 mg/kg), high dose of root extract of Achyranthe saspera (500 mg/kg), metformin (250 mg/kg), resp. treated for 35 days. Body weight followed by serum glucose, insulin, HBA1C, HOMA- IR, serum lipid profile, and liver glycogen were evaluated. HFD + Diabetic group showed an elevated level of lipid profile and alterations in serum glucose, HbA1C, HOMAIR, Insulin and liver glycogen. Administration of Metformin and hydro alc. root extract of Achyranthes aspera500 mg/kg to HFD + diabetic group protected the biochem. alterations and serum insulin, glucose levels, HbA1c, HOMA- IR, liver glycogen. In comparison with HFD group, there was 1.76,2.02, and,1.3-fold decrease in Glucose levels in HFD+STZ+ Metformin, HFD+STZ+HEAA250, and HFD+STZ+HEAA500 groups resp. In comparison with HFD group, there was a 1.38,1.15 and,1.59-fold increase in Insulin levels in HFD+STZ+ Metformin, HFD+STZ+HEAA250, and HFD+STZ+HEAA500 groups resp. The HbA1C levels (mean±SEM) of control, STZ, HFD+STZ, HFD+STZ+ Metformin, HFD+STZ+HEAA250, and HFD+STZ+HEAA500 were 7.36±0.22,10.18±0.74,8.94±0.33,8.10±0.22,8.94±0.22 and 7.0±0.41 resp. The HOMA-IR levels (mean±SEM) of control, STZ, HFD+STZ, HFD+STZ+ Metformin, HFD+STZ+HEAA250, andHFD+STZ+HEAA500were 2.08±0.12,3.99±0.85,17.05±3.53,1.61±0.28,2.46±0.74 and 2.01±0.20 resp. The study findings reveal the protective role of Achyranthesaspera on high-fat diet and a diabetic induced biochem. changes.