Background: Lifestyle changes can reduce the risk of T2D; however, no study has evaluated the effect of a lifestyle intervention involving patients´family. The aim of this study was to compare the impact of an interdisciplinary family (FI) Vs individual intervention (II) on glucose metabolism, insulin resistance (IR), pancreatic β-cell function and cardiovascular risk markers in patients with prediabetes, as well as to measure the impact on their families' metabolic risk. Methods: Randomized Clinical Trial (RCT) to compare the impact of FI and II on IR and pancreatic β-cell function in subjects with prediabetes. There were 122 subjects with prediabetes (and 101 family members) randomized to FI or II. Data were collected in 2015-2016 and analyzed in 2017-2018. FI group had the support of their family members, who also received personalized diet and exercise recommendations; patients and their family members attended monthly a lifestyle enhancement program. II group received personalized diet and exercise recommendations. The follow-up was for 12 months. Glucose, IR, pancreatic β-cell function and secondary outcomes (body composition and lipid profile) were assessed at baseline, 6 and 12 months. Results: FI group improved area under the glucose curve (AUC) (from 18,597 ± 2611 to 17,237 ± 2792, p = 0.004) and the Matsuda index (from 3.5 ± 2.3 to 4.7 ± 3.5, p = 0.05) at 12 months. II group improved Disposition Index (from 1.5 ± 0.4 to 1.9 ± 0.73, p < .0001) at 12 months. The improvements achieved in weight and lipids at 6 months, were lost in II group at 12 moths, whereas in FI persisted. Adherence up to 12 months was not different between the study groups (FI 56% Vs II 60%). Conclusions: FI intervention was more effective by improving glucose AUC, insulin sensitivity and lipid profile, besides that, metabolic risk in family members of the FI group was maintained, while the risk of II group was increased. Trial registration: This study was retrospectively registered at clinicaltrials.gov on December 15, 2015 (NTC026365646).