BACKGROUND In this study, the duration of high‐pressure processing (HPP) required to achieve a 5 log reduction of Escherichia coli O157:H7 in fruit purees was evaluated. Banana, cantaloupe, and dragon fruit purees were subjected to HPP at 600 MPa for 300, 270, and 270 s, respectively, and their physicochemical properties and enzyme activities were then analysed. Diabetic mice were fed fresh and HPP‐treated purees to observe their effects on the glycemic index (GI) and postprandial blood glucose response. RESULTS Compared with their fresh counterparts, the HPP‐treated banana and dragon fruit purees exhibited significantly higher viscosities, lower glucose concentrations, and higher glucose dialysis retardation indices and showed disrupted sucrose invertase and polygalacturonase activities. The GI and postprandial blood glucose response were not significantly different between the fresh and HPP‐treated cantaloupe purees. By contrast, the peak time of glucose response (Tmax) was delayed from 30 min to 60 min, and the area under the receiver operating characteristic curve was reduced by 40% in the mice fed HPP‐treated banana and dragon fruit purees. The GIs of the HPP‐treated banana and dragon fruit purees (were 50.3 and 44.8, respectively) were significantly lower than those of their fresh counterparts (85.1 and 75.2, respectively). CONCLUSION HPP can change the physicochemical properties of fruit purees, resulting in stabilized blood glucose levels and lower GIs after consumption. Therefore, purees processed in this manner would benefit consumers and patients with diabetes/pre‐diabetes who need to maintain stable blood glucose levels (Fig. S1). © 2022 Society of Chemical Industry.