Background: Diabetes mellitus is a chronic overwhelming disease that is treated with insulin. Subcutaneous insulin injection has several drawbacks such as nerve damage, microbial contamination, thermal instability, and pain. Exogenous insulin is essential in the management of type 1 diabetes and plays a complementary role in the management of type 2 diabetes, where oral hypoglycemic agents play a major role in treatment. Pain, injection site lipodystrophy, nerve damage, thermal instability, and microbial contamination during injection are the major side effects of insulin administered via the IV or SC route. Aim: Formulation of recombinant oral human insulin tablets by bioinformatics and peptidomimetics. Methods: In this study, insulin was produced by recombinant DNA technology using bioinformatics. Protease inhibitors and polymeric adhesives were added to enteric-coated insulin tablets for oral insulin. Test insulin was tested in animal models and compared to standard subcutaneous insulin for efficacy. Human insulin tablets were made by a wet granulation process with varying concentrations of starch, sucrose, talc, and sodium carboxymethylcellulose. DSC and FTIR spectroscopy were used for drug and polymer compatibility studies. A pre-formulation characterization of the active ingredient (API) was performed. Similarly, post-compression parameters such as wetting time, disintegration time, in vivo bioavailability, in vitro drug release, and water absorption studies of optimized formulations were evaluated. Results: In this study, we designed and developed insulin that can be formulated as an oral drug delivery system. The efficacy of the experimental insulin was nearly 60% in Phases 1/2 human clinical trials. Conclusion: New insulin tablet formulations helped overcome the drawbacks of subcutaneous injections of insulin.