Artificial sweeteners have been in use by food industries for a long time. Safety concerns raised about artificial sweeteners since they are widely used nowadays. The present work aims to study the possible changes in body weight, blood picture, liver functions, blood glucose and liver glycogen content as well as histopathological changes induced in liver and urinary bladder of male albino rats after administration of two artificial sweeteners (saccharin or aspartame). Male rats were administered saccharin (50 mg/kg b.w.) or aspartame (100 mg/kg b.w.) daily by intragastric gavage for 14 weeks. The results revealed that both saccharin and aspartame provoked highly significant reduction in body weight gain %. Saccharin exerted highly significant reduction in haemoglobin (Hb) level, haematocrit (Hct%) and red blood cells (RBCs) count, while aspartame induced insignificant changes in all haematological parameters. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity levels were significantly increased with saccharin and aspartame. Alkaline phosphatase (ALP) levels in serum showed slightly insignificant increase by saccharim administration, while aspartame caused a significant rise in ALP. Blood glucose level of rats given saccharin significantly dropped, while aspartame caused a significant elevation in blood glucose level. Liver glycogen content of rats given saccharin significantly increased, while aspartame caused a significant reduction in liver glycogen content. Microscopic examination of liver sections showed lymphocytic and macrophages infiltration of the portal traid in rats administered saccharin, while aspartame group showed no histopathological changes except slight hydropic degeneration of hepatocytes. Urinary bladder sections of rats administered saccharin revealed proliferation of the mucosal epithelial cells into papillary invaginated projections with highly vascularized connective tissue core and mononuclear inflammatory cells infiltration, while aspartame group showed no histopahtological alterations. It could be recommended that the use of saccharin as an artificial sweetener should be restricted, while aspartame should not be administered to diabetic. When it is necessary to use artificial sweeteners, fresh fruits and vegetables should be ingested as they act as scavengers for the liberated free radicals and help to delay the postprandial rise in blood glucose level.