A challenge design was used in eight Separate studies using young adult male albino rats (mean weight + 69.5g) to investigate the effects of natural; non-nutritive sweeteners ingestion on weight gain, food intake and clinical biochemical parameters. The result revealed that, the patterns in feed consumption were less clear than the growth data. For the sucrose diet, the rats receiving added either saccharin, or aspartame had significantly smaller weight gains than did the corresponding sucorse group. Rats fed saccharin diet incorporated with aspartame; and with sucrose, consumed. diet than did the corresponsing saccharin group, while gaining a smaller amount of weight. All organs weights Were reduced in aspartame and saccharin groups (except liver) than did the corresponding rats served as controls. Serum total protein concentration was reduced with an increase in urea level, while creatinine did not show any significant changes. There was a significant relationship between dietary regimen and serum total lipids and triacylglycerols. Also there was Significant decrease in the activities of ASAT (S.Got) in all experimental rats group, except in saccharin regimen group, on the other hand, there were significant elevations in ALAT (S.GPT) activities in all experimental rat groups than did the corresponding control group. Using the casein diet, there was significant differences in liver total protein (P<0.05) and glycogen (P<0.01) concentration between animals on aspartame: Saccharin diet (9.362/100g tissue); (49.98 mg/100g tissue), and those on sucrose: aspartame (7.57g/100g tissue; 59.8 mg/100 g tissue) respectively. The examined brain sections in rats receiving aspartame:saccharin mixture in a 1:3 ratio, showed necrosis cellularity (stage of tumors). Numerous questions remain unanswered, particularly with respect to the possible effects of aspartame on human beings who may consume the compound over years of daily use.