PurposeTo investigate the mediating role of general self‐efficacy (i.e., belief in one's competence to cope with a broad range of stressful or challenging demands) in the relationship between adverse childhood experiences (ACEs) and psychological distress (i.e., symptoms of stress, anxiety and depression) in gender minority individuals, which include people with a gender identity that is not aligned with their sex assigned at birth.Design and methodsThe study sample included gender minority participants who participated in Waves 4 and 5 of Project AFFIRM, a multi‐site longitudinal study of gender minority health. ACEs, general self‐efficacy, and psychological distress were measured using the Behavior Risk Factor Surveillance System ACE Module at Wave 4, the PROMIS General self‐efficacy measure at Wave 4, and the Brief Symptoms Inventory Global Severity Index (GSI) at Wave 5, respectively. After adjustment for covariates, including age, race, sex assigned at birth, and income, multivariable linear regression analyses were conducted to assess each component of the proposed mediation model. Next, mediation analyses were used to determine whether general self‐efficacy mediated the association between ACEs and psychological distress.FindingsThe sample for this study consisted of 166 gender minority adults with a mean age of 38.6 ± 12.2 years. Most were non‐Hispanic White (46.4%) and female assigned at birth (59.6%). Mean ACEs score was 3.2 ± 2.1 (range 0–8), mean general self‐efficacy score was 13.9 ± 3.6 (range 4–20), and mean raw‐score GSI was 17.3 ± 13.7 (range 0–64). Participants who reported experiencing more ACEs had greater psychological distress (B 1.60; 95% CI = 0.66, 2.54) and lower general self‐efficacy (B −0.41; 95% CI = −0.67, −0.15). In addition, lower general self‐efficacy was associated with higher psychological distress (B −1.06; 95% CI = −1.61, −0.51). Bootstrap estimation of the indirect effect was significant (95% CI = 0.14, 0.90) and explained 27.1% (95% CI = 7.76, 69.76) of the total effect of ACEs on psychological distress in gender minority adults.ConclusionsOur findings suggest that general self‐efficacy partially mediated the positive association between ACEs and psychological distress in gender minority adults. Interventions that aim to improve general self‐efficacy may be beneficial in alleviating psychological distress in gender minority adults.Clinical relevanceNurses can play an important role in reducing the health risks associated with ACEs by screening gender minority individuals using a trauma‐informed approach to care and offering resources and referrals, as appropriate.