Background: Non-nutritive sweeteners (NNSs) are becoming popular as sugar substitutes for diabetic patients or to decrease body weight. Aim of the work: This study was aimed to determine the effects of sucralose and sodium saccharin on some physiological parameters in male albino rats. Materials and methods: We used thirty male albino rats weighing from 100 to120 gm. The period of the experiment was 30 days. The animals were divided into three groups; Group 1: control, Group 2: rats received sucralose and group 3: rats received sodium saccharin. The following parameters were processed: serum glucose, ASAT, ALAT, serum creatinine, serum urea, protein and lipid profiles and hormonal levels (insulin, testosterone, serum T3 and T4). Results: There was an increase in ASAT and ALAT activities, serum creatinine and serum urea levels in group 2 and group 3, lipid profile in the group received sucralose (TC and HDL) and T3&T4 in the group received saccharin as compared to the control group. Meanwhile, a drop in serum glucose, insulin, total protein, albumin, albumin/globulin ratio and triglycerides in group 2 and group 3, lipid profile in the group received saccharin (TC and HDL) and T3&T4 in the group received sucralose was observed when compared to the control group. Conclusion: it could be concluded that sucralose and sodium saccharin must be carefully used because they have very dangerous effects-especially sodium saccharin- and we have to replace them with natural sugar.