AbstractObjectiveThe aim of this study was to test the effects of repetitive active transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex (rDLPFC) associated with a hypocaloric diet on glucose homeostasis in people with excessive weight.MethodsAdults with overweight or obesity were selected in a randomized, double‐blind pilot study to complete 4 weeks (20 sessions) of fixed‐dose tDCS (2 mA, 20 minutes) delivered over the rDLPFC and associated with a standard hypocaloric diet. Participants were randomly assigned (1:1) and stratified by sex to the active tDCS group (active) or the sham tDCS group (sham). Changes in glucose homeostasis were assessed in a 4‐hour liquid meal tolerance test, performed before and after the intervention.ResultsTwenty‐eight participants were randomized (79% with obesity; mean [SD] age 37.6 [5.8] years). After the intervention, fasting plasma glucose (mean [95% CI], −7.8 mg/dL [−14.0 to −1.6]) and insulin levels (−7.7 μIU/mL [−13.9 to −1.6]) decreased in the active compared with the sham. Similarly, the Matsuda insulin sensitivity index increase in the active (4.7 pmol⁻¹ × mmol⁻¹ [1.6 to 7.8]) compared with the sham (0.6 pmol⁻¹ × mmol⁻¹ [−1.4 to 3.2]).ConclusionsRepetitive, active tDCS over the rDLPFC could be a promising noninvasive technique to improve glucose homeostasis in individuals with overweight or obesity on a low‐calorie diet, highlighting the importance of investigating this intervention modality in individuals with type 2 diabetes mellitus.