Introduction and Aim: This study is to evaluate the levels of paraoxonase-1 and visfatin in diabetic and diabetic with hypothyroidism patients and to discover the relationship of paraoxonase-1 and visfatin levels in these patients. Materials and Methods: The study included 35 subjects in control group (G1), 35 with diabetes (G2), and 35 diabetes with hypothyroidism (G3), aged ranging 25-50 years for all the study groups and BMI with (20.5-25.4) Kg/m2. Serum and whole blood were used for estimating F.B.S., HbA1c%, lipid profile, T4, TSH, paraoxonase-1 and visfatin. Results: The results revealed a significant elevation in F.B.S., HbA1c%, TC, TG, VLDL and LDL in G2 and G3 compared to G1.   The HDL levels showed a significant decrease in G2, G3 compared to G1. Also, showed significant reduction in T4 in G3 compared to G2 and G1. A significant elevation in TSH in G3 compared to G2 and G1 and a significant decrease in paraoxonase-1 but increase in visfatin for G3 more than G2 when compared to G1 were observed. Conclusion:  The study concluded that paraoxonase -1 and visfatin are suggestive reliable markers for the diagnosis of thyroid disorder in diabetics with hypothyroidism depending on their relation with T4 and TSH.