The development of food-grade carriers based on EFSA and/or FDA-approved polymeric materials is an area of growing interest for the targeted delivery of bioactive compounds to the colon. Many nutraceuticals have shown promise in the local treatment of conditions that threaten quality of life, such as ulcerative colitis, Crohn’s disease, colorectal cancer, dysbiosis and other problems affecting the gut and colon. Nevertheless, their bioavailability is often limited due to poor solubility, rapid metabolism and low permeability, as well as undesirable local side effects. Encapsulation in carriers, which can protect the active ingredient from degradation and improve absorption and targeted administration in the colon, is one way to overcome these limitations. The technological characterization of these systems is important to assess their efficacy, safety and stability. In particular, morphology, size and surface properties influence their actions and interaction with the bio-phase. Meanwhile, encapsulation efficiency, profile and in vitro release kinetics are key parameters to assess the ability to reach the target site. This paper proposes a recent review of food-grade polymer-based systems for colorectal targeting of bioactive substances, focusing on their technological characterization and assessment of stability and biological activity, which are important in determining their full bench-to-bed potential.