Common bean (Phaseolus vulgaris L.) is a good source of protein, vitamins, minerals and complex carbohydrates. The objective was to compare protein profile, including anti-nutrient proteins, and potential bioactive peptides of improved common bean cultivars grown in Mexico and Brazil. Bean protein isolates (BPI) were prepared from 15 common bean cultivars and hydrolyzed using pepsin/pancreatin. Thirteen proteins were identified by SDS-PAGE and protein in-gel tryptic-digestion-LC/MS. Protein profile was similar among common bean cultivars with high concentrations of defense-related proteins. Major identified proteins were phaseolin, lectin, protease and α-amylase inhibitors. Lectin (159.2 to 357.9 mg lectin/g BPI), Kunitz trypsin inhibitor (inh) (4.3 to 75.5 mg trypsin inh/g BPI), Bowman-Birk inhibitor (5.4 to 14.3 μg trypsin-chymotrypsin inh/g BPI) and α-amylase inhibitor activity (2.5 to 14.9% inhibition relative to acarbose/mg BPI) were higher in Mexican beans compared to Brazilian beans. Abundant peptides were identified by HPLC-MS/MS with molecular masses ranging from 300 to 1500 Da and significant sequences were SGAM, DSSG, LLAH, YVAT, EPTE and KPKL. Potential bioactivities of sequenced peptides were angiotensin converting enzyme inhibitor (ACE), dipeptidyl peptidase IV inhibitor (DPP-IV) and antioxidant capacity. Peptides from common bean proteins presented potential biological activities related to control of hypertension and type-2 diabetes.