Amiodarone (AMD), an antiarrhythmic drug, causes side effects in multiple organs. S-methylmethionine sulfonium (vitamin U, Vit U) has potential protective effects against these adverse outcomes. The objective of this study was to investigate the effects of AMD and Vit U on rat parotid salivary glands. The rats were assigned to four groups: control (corn oil for 7 days), Vit U (50 mg/kg/day for 7 days), AMD (100 mg/kg/day for 7 days), and AMD+Vit U (combined AMD and Vit U for 7 days). On day 8, parotid glands were collected for analysis of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), thromboplastic activitiy (TrA), lipid peroxidation (LPO), myeloperoxidase (MPO), sodium-potassium ATPase (Na+/K+- ATPase), sialic acid (SA), hexose, hexosamine, fucose and total protein (TP). AMD administration significantly increased the values of GSH, LPO, MPO and hexosamine while decreasing the values of Na+/K+-ATPase, SA and hexose compared to controls. Co-administration of Vit U with AMD reversed these changes, indicating that Vit U may help to reduce AMD-induced oxidative stress in the parotid salivary gland and restore altered biochemical parameters. 7-day treatment with AMD induced oxidative damage and inflammation in the parotid gland. Vit U showed protective effects, especially in reducing oxidative damage, inflammation and glycosylation changes.