Given the disproportionate alcohol-related consequences experienced by North American Indigenous youth, there is a critical need to identify related risk and protective factors. Self-compassion, which has been found to mitigate the effects of trauma exposure, may serve as one such protective factor given the high degree of historical trauma and contemporary discrimination identified as contributing to the alcohol-related disparities experienced by Indigenous communities. However, no research has examined how self-compassion (i.e. the ability to be kind and accepting and to extend compassion toward oneself) plays a unique role in Indigenous peoples’ experiences with alcohol. First Nation adolescents between the ages of 11 and 18 living on a reserve in Eastern Canada (N = 106, Mage = 14.6, 50.0% female) completed a pencil-and-paper survey regarding their alcohol use, alcohol-related problems, and self-compassion. Self-compassion was significantly inversely associated with alcohol-related problems (b = -.51, p = .01, 95%CI [-.90, −.12], and significantly interacted with frequency of alcohol use in predicting alcohol-related problems (b = -.42, p = .04, 95%CI [-.82, −.03]). Simple slopes analyses revealed that the association between frequency of alcohol use and frequency of experiencing alcohol-related problems was significant and positive at low (b = 4.68, p < .001, 95%CI [2.62, 6.73]), but was not significant at high (b = -.29, p = .89, 95%CI [−4.35, 3.77]) levels of self-compassion. Binary logistic regression revealed that higher scores of self-compassion were associated with a lower odds of being in the high-risk group for AUD (OR = 0.90, 95%CI [0.83, 0.98], p = .02). Our results suggest self-compassion may be protective against experiencing alcohol problems in Indigenous youth and thus may be a target for behavioral interventions.