Loneliness has been linked to impairment in emotional appraisal and emotion regulation. This study aimed to test a set of pre-registered hypotheses by suggesting that loneliness alters bottom-up appraisal processes of social threat and top-down emotion regulation mechanisms. In this double-blind, within-subject study, we included 120 individuals (equally split between highly lonely and non-lonely groups) who received active (2 mA) or sham transcranial direct current stimulation over the left or right dorsolateral prefrontal cortex (dlPFC) in separate sessions. Participants were asked to passively watch negative or neutral stimuli or to reinterpret negative stimuli to decrease their affective response. Overt behavioral responses (valence and arousal self-response) and covert physiological markers (event-related potentials [ERPs]) of the affective response in each group were analyzed separately for stimuli with and without social content. Active dlPFC stimulation enhanced neural modulation during the reappraisal of social stimuli, as reflected in a larger difference in late positive potential between reappraised and passively viewed negative images. However, the valence rating difference between these conditions suggested less effective reappraisal under active stimulation. Anodal stimulation of the left dlPFC selectively decreased self-reported emotional reactivity during the passive viewing of social stimuli in highly lonely individuals. However, this effect occurred without corresponding changes in ERP markers. Loneliness may primarily impair the self-monitoring of affective responses rather than that of regulatory mechanisms. The left dlPFC supports the accurate self-assessment of emotional states, and targeted non-invasive brain stimulation can alleviate loneliness-related difficulties in this domain.