Abstract: Provided herein are compositions and methods to enhance the absorption of S-adenosylmethionine (SAMe) and methods of treating various disorders or diseases using non-parenteral SAMe formulations with enhanced-absorption and improved bioavailability. In certain embodiments, the enhanced bioavailability formulations provided herein may be used to treat a variety of diseases or disorders, such as for example, psychiatric disorders including, generalized anxiety disorder, obsessive compulsive disorder, post traumatic stress disorder, panic disorder, depressive disorders (e.g. major clinical depression) and dysthymia; as well as treating liver disorders, cancer, autoimmune disorders, inflammatory disorders, joint disorders, gastrointestinal disorders and cardiovascular disease.