To investigate the effect of curcumin on the multivariate and docking analysis on peroxisome proliferator activated receptor-γ, the rats were fed with high fructose diet (Group 2) to induce insulin resistance and curcumin was co-administered orally (Group 4) for a period of 8 weeks and measured the biochemical parameters in blood, kidney and liver tissues. The results showed a significant (p ≤ 0.05) increase in the level of creatinine, glucose, insulin, low density lipoprotein, total cholesterol, triglyceride, urea, uric acid, very low density lipoprotein and decreased albumin, high density lipoprotein and total protein level in the blood of Group 2 when compared with Group 1 control rats. Further, analysis on liver and kidney tissues showed a significant decrease in antioxidants, hexokinase and increased glucose 6-phosphatase and fructose 1,6-bisphosphatase, hydroperoxides and TBARS in Group 2 rats. Furthermore, the multivariate and loading coefficient analysis showed that albumin, HDL, catalase, glutathione reductase, hexokinase and vitamin E are the most contributing factors in blood, liver and kidney. Subsequently, molecular docking was carried out to determine the binding efficiency of curcumin as agonist of PPARγ showed high affinity compared to pioglitazone. The histology of liver and kidney were also studied and the administration of curcumin along with fructose protects the organs from the abnormal changes and also prevents the fat accumulation. Overall, these results demonstrate the preventive role of curcumin on diet induced insulin resistant in rats by ameliorating the altered levels of metabolic changes and potential binding of curcumin with PPARγ as agonist in the treatment of insulin resistance.