Insulin, a pivotal anabolic hormone, regulates glucose homeostasis by facilitating the conversion of blood glucose to energy or storage. Dysfunction in insulin activity, often associated with pancreatic β cells impairment, leads to hyperglycemia, a hallmark of diabetes. Type 1 diabetes (T1D) results from autoimmune destruction of β cells, while type 2 diabetes (T2D) stems from genetic, environmental, and lifestyle factors causing β cell dysfunction and insulin resistance. Currently, insulin therapy is used for most of the cases of T1D, while it is used only in a few persistent cases of T2D, often supplemented with dietary and lifestyle changes. The key challenge in oral insulin delivery lies in overcoming gastrointestinal (GI) barriers, including enzymatic degradation, low permeability, food interactions, low bioavailability, and long-term safety concerns. The muco-adhesive (MA) and muco-penetrative (MP) formulations aim to enhance oral insulin delivery by addressing these challenges. The mucus layer, a hydrogel matrix covering epithelial cells in the GI tract, poses significant barriers to oral insulin absorption. Its structure, composition, and turnover rate influence interactions with insulin and other drug carriers. Some of the few factors that influence mucoadhesion and mucopenetration are particle size, surface charge distribution, and surface modifications. This review discusses the challenges associated with oral insulin delivery, explores the properties of mucus, and evaluates the strategies for achieving excellent MA and MP formulations, focusing on nanotechnologybased approaches. The development of effective oral insulin formulations holds the potential to revolutionize diabetes management, providing patients with a more convenient and patient-friendly alternative to traditional insulin administration methods.