Background: Several plant peptides have been known to exhibit various pharmacological activities. However, the bioactivity of mulberry peptides is not yet reported. Objective: In the present study, the peptides from different mulberry cultivars, namely S1, V1, S1635, and Dudhiya, were isolated and assessed for their in vitro free radical scavenging capacity and inhibitory activity of two key enzymes (α-amylase [AA] and α-glucosidase [AG]) associated with type-II diabetes. Materials and Methods: The 0.5-3 kDa ranged oligopeptides were isolated using cation exchange chromatography and ultrafiltration system and further characterized by high-performance liquid chromatography and protein sequencer. The peptides were investigated for their in vitro antioxidant potential by 1,1-diphenyl-2 picrylhydrazyl, 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, and nitric oxide scavenging capacity and reducing power, metal chelating, and anti-lipid peroxidation activity along with in vitro antidiabetic activity by AA and AG inhibition. Results: The results revealed that the peptides were found to possess significant free radical scavenging as well as AA and AG inhibitory activity in a dose-dependent manner. Overall, the peptide isolated from S1 cultivar exhibited the most promising therapeutic potential. Further, the variation in amino acid composition of the oligopeptides could be associated with the observed variation in their bioactivity. Conclusion: These natural peptides may constitute an important part of the antioxidant defense system as well as antidiabetic agent and further could be used for the formulation of functional food and nutraceuticals. © 2018 Pharmacognosy Research Published by Wolters Kluwer - Medknow.