For patients, taking medication orally is the simplest and most convenient way to do so. It is also typically the safest and least expensive option. The oral medication delivery industry is the largest segment of the entire drug delivery business from a commercial standpoint. The oral route is not without considerable difficulties, though. We start by thinking about the GI tract's structure and physiology, as well as the implications for successful oral medication administration and the considerations that must be made when building effective oral Drug Delivery Systems (DDS). The topic of oral controlled-release (CR) technology is then discussed, starting with the hydrophilic matrix tablet, which is the most popular and effective oral CR technology. There structures that are diffusion- and/or dissolution-controlled. Regional targeting of drugs inside the GI tract is reviewed, including medication targeting to the colon and small intestine (SI) via gastroprotection in the stomach.