The current study examined whether Religion/Spirituality (R/S) or mindfulness-based interventions attenuate negative emotional experiences and concomitant physiological responses via emotion regulation. Secondary aims examined whether trait levels of R/S or mindfulness influenced affective and physiological responding over and above the interventions. Participants (Mage = 21.301 ± 3.588) were randomly assigned to either a R/S or mindfulness intervention, or a control condition. R/S (n = 28) or mindfulness (n = 26) intervention groups were required to Decrease (i.e., attenuate) affective responses to negative images via cognitive reappraisals drawn from a biblical excerpt or poem, respectively. Control participants (n = 29) were instructed to Maintain their emotions (i.e., respond naturally). Paired T-tests constrained to the Control group indicated that negative picture blocks were rated higher on average arousal (t(27) = 10.042, p < .001), valence (t(27) = 11.298, p < .001), and state NA (t(27) = 8.500, p < .001) compared to neutral-blocks. Tests of the primary aims were restricted to the Decrease or Maintain -negative picture blocks viewed by the intervention groups. Results of the repeated measures mixed-ANOVAs revealed that average arousal (F(1) = 91.021, p < .0005), valence (F(1) = 63.225, p < .0005), and state NA (F(1) = 30.167, p < .0005) ratings were significantly lower for the Decrease-negative picture blocks compared to the Maintain-negative blocks. Furthermore, average respiration rate (F(1) = 8.821, p = .005) was also significantly lower for Decrease-negative pictures, but average heart rate was unaffected . Trait effects were also NS. Results indicate that emotion regulation potentially undergirds the effects of R/S or mindfulness-based coping. Notably, NS differences between intervention-type suggests the approaches are comparable.