Diabetes is a disorder that impairs the ability of the body to process blood glucose. Diabetes is either due to the pancreas produces insufficient amount of insulin or the cells of the body do not react with the insulin produced. Type 2 diabetes (diabetes mellitus) is the most common type of diabetes and grows in prevalence worldwide. The aim of our study was to investigate the anti-diabetic impact with emphasis on hepatic lipid metabolism and spleen histopathology effect of curcumin-magnesium oxide nanoparticles conjugate (Cur-MgO NPs conjugate) in nicotinamide (NA)-streptozotocin (STZ) induced type 2 diabetic rats. This study included three groups: Group 1 (control group), Group 2 (STZ induced type 2 diabetic rats) and Group 3 (type 2 diabetic rats were orally administered Cur-MgO NPs conjugate (10 mg/Kg BW/day for 45 days)). The levels of plasma glucose, serum insulin, lipid profile and hepatic expression of lipogenic enzymes Malonyl-CoA decarboxylase (MCD), Peroxisome proliferator-activated receptor alpha (Ppar α) were measured. Moreover, histopathological examination of spleen was carried out. The assessment of Insulin Resistance (HOMA-IR), a significant reduction in serum insulin level and HOMA of β-cell function (HOMA β). Also, reduction in hepatic mRNA expression of MCD and Ppar-α and an altered lipid profile were noticed in diabetic group in comparison with the control group. Oral administration of Cur-MgO NPs conjugate restored glucose (102.73±2.16), TC (139.80±3.61) and LDL-c (87.56±3.72) to their physiological levels in the control group (108.29±2.45, 150.27±2.56 and 94.43±2.75 respectively). Histopathological examination of the spleen showed damage of lymphoid cells in type 2 diabetes (T2D), while in treated group showed moderate improvement in spleen tissue and cells are rescued from apoptosis. The outcome of present study revealed that Cur-MgO NP conjugate has potential ameliorative effect on the hematologic, immunologic and hepatic metabolic alterations in type 2 diabetic rats.