BACKGROUND: Compassion motivation is associated with increased heart rate variability (HRV), reflecting a calm and self-soothing physiological state. Recent work, however, suggests that this association is dynamic for the specific components of compassion. OBJECTIVES: The present study adopted anodal transcranial direct current stimulation (tDCS) targeting the right insula to see whether this would modulate the sensitivity to suffering and the commitment to engage in helpful actions (i.e., the components of compassion motivation). METHOD: Ninety-seven healthy individuals underwent 15-min anodal or sham tDCS over the frontotemporal lobe, while watching a video inducing empathic sensitivity and performing a Redistribution Game. Tonic and phasic HRV, dispositional traits, and momentary affects were assessed. RESULTS: Compared to sham condition, anodal stimulation favored significant i) HRV reductions during the video and HRV increases during the Redistribution Game; ii) decreases in self-reported levels of negative affect and increases in positive affect during task when the latter was preceded by the video, without influencing altruistic behavior. CONCLUSIONS: Anodal tDCS over the right insula may modulate the engagement phase of compassion by intensifying the psychophysiological sensitivity to signals of distress and protecting from being subjectively overwhelmed by it.