The objective of this study was to evaluate and compare the effect of peptides produced from hard-to-cook common bean proteins on insulin secretion from pancreatic β-cells and glucose uptake from insulin-resistant adipocytes, and to understand the mechanism of action on markers related to glucose metabolism, in vitro. Hydrolysates and peptide fractions < 1 kDa of two common bean varieties (pinto Durango and black 8025) were produced with alcalase and bromelain, and were further hydrolysed with pepsin-pancreatin to simulate gastrointestinal tract digestion. All bean treatments were able to increase glucose-stimulated insulin secretion from rat insulinoma INS-1E cells, reduced the expression of proteins like dipeptidyl peptidase IV (DPP-IV) and receptor for advanced glycation end products (RAGE) and significantly reduced oxygen species (up to 70%). Peptides also inhibited lipid accumulation in mature adipocytes 3T3-L1 and increased glucose uptake (67%) via Akt modulation in insulin resistant adipocytes enhancing insulin signalling and reducing the phosphatase and tensin homologue (PTEN) activation.