Nanotechnology has emerged as a promising avenue for targeted drug delivery to the small intestine, offering precise control over drug release and enhanced therapeutic efficacy. This review discusses recent advancements and challenges in nanotechnology-based approaches for targeted drug delivery to the small intestine. The small intestine presents unique challenges for drug delivery, including enzymatic degradation, low permeability, and rapid transit time. Nanotechnology offers solutions to these challenges by providing carriers capable of protecting drugs from degradation, enhancing their absorption, and facilitating site-specific delivery. Various nanocarrier systems have been explored for targeted drug delivery to the small intestine, including liposomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles. These carriers can be functionalized with ligands targeting specific receptors or transporters expressed on the intestinal epithelium, enabling efficient uptake and intracellular delivery of drugs. Additionally, nanotechnology enables the controlled release of drugs, allowing for sustained and/or triggered release profiles tailored to the physiological conditions of the small intestine. This precise control over drug release can improve therapeutic outcomes while minimizing systemic side effects. Despite the significant progress in nanotechnology-based drug delivery to the small intestine, several challenges remain. These include achieving sufficient drug loading capacity, ensuring biocompatibility and safety of nanocarriers, and addressing regulatory concerns associated with their clinical translation. In conclusion, nanotechnology holds immense potential for targeted drug delivery to the small intestine, offering solutions to overcome the limitations of conventional drug delivery systems. Addressing the remaining challenges will be crucial for realizing the full therapeutic benefits of nanotechnology in treating diseases affecting the small intestine.