The growing interest in bioactive compounds, especially in polyphenols, is due to their abundance in the human diet and potentially positive effects on health. The consumption of polyphenols has been shown to possess anti-diabetic properties by preventing insulin resistance or insulin secretion through different signaling pathways, this effect is associated with their capacity to exert genomic modulations. Several studies have suggested that polyphenols could also bind to cellular proteins and modulate their activity, however, the mechanisms of action underlying their beneficial effects are complex and are not fully understood. The aim of this work was to characterize phenolic compounds present in blue corn and black bean extracts as well as identify their potential interactions with target proteins involved in diabetes pathogenesis using in silico approach. Total polyphenols content of both blue corn and black beans was identified using UPLC-ESI/qTOF/MS and quantified by colorimetric assays. In this work we identified twenty-eight phenolic compounds in the extracts, mainly anthocyanins, flavonols, hydroxycinamic acids, dihydroxybenzoic acids, flavones, isoflavones, and flavanols. Interactome of these compounds with thirteen target proteins involved in type 2 diabetes mellitus was performed in-silico. In total, 312 bioactive compounds/protein interaction analyses were acquired. Molecular docking results highlighted that nine of the top ten interactions correspond to anthocyanins, cyanidin 3-glucoside with 11β-HS, GFAT, PPARG; delphinidin 3-glucoside with 11β-HS, GFAT, PTP and RTKs; and petunidin 3-glucoside with 11β-HS and PTP. These proteins are involved in mechanisms regulating functions such as inflammation, insulin resistance, oxidative stress, glucose and lipid metabolism. In conclusion, this work provides a prediction of the potential molecular mechanism of black bean and blue corn polyphenols, specifically anthocyanins and could constitute new pathways by which compounds exert their antidiabetic benefits.