This study aimed to investigate the effect of replacing corn starch in the standard diet of diabetic hypercholesterolemic rats with 3, 6 and 9% levels of honeydew melon fruit powder, peeled honeydew melon fruit powder and honeydew melon peels powder (melon fractions) on the body weight gain, insulin, organs weight, blood glucose, total cholesterol, LDL, triglyceride, kidney functions, liver functions, catalase enzyme, glutathione S-transferase enzyme and malondialdehyde. Data showed diabetes and hypercholesterolemia caused a significant increase in body weight gain, organs weight, blood glucose, total cholesterol, LDL, triglyceride, kidney functions, liver functions and malondialdehyde as well as a significant decrease in insulin, catalase enzyme and glutathione S-transferase enzyme of rats. The feeding with any level of melon fractions restored the normal liver weight and AST level in diabetic hypercholesterolemic rats to the normal values in negative control rats. Also, feeding with 9% melon fractions restored the normal body weight gain, insulin, kidney weight, heart weight, urea, creatinine, ALT, catalase enzyme, glutathione S-transferase enzyme and malondialdehyde in diabetic hypercholesterolemic rats to the normal values in negative control rats. Although glucose, total cholesterol, LDL, triglyceride, and ALP in diabetic hypercholesterolemic rats were decreased by increasing the melon fraction levels but did not return to normal values in negative control rats.