Background: Potential associations between dietary glycemic index (GI) and glycemic load (GL) with psychological disorders remain uncertain. Objective: We investigated the relations of dietary GI and GL with psychological distress, anxiety, and depression. Design: A total of 3363 nonacademic members of the staff of Isfahan University of Medical Sciences were included in this cross-sectional study. GI and GL were assessed by using a validated, self-administered, dish-based, semiquantitative food-frequency questionnaire. Validated Iranian versions of the Hospital Anxiety and Depression Scale and General Health Questionnaire-12 were used to assess anxiety, depression, and psychological distress. Results: After control for potential confounders, individuals in the top tertile of GI had greater odds of depression (OR: 1.44; 95% CI: 1.03, 2.02; P-trend = 0.03) and a trend for greater odds of anxiety (OR: 1.52; 95% CI: 0.97, 2.38; P trend = 0.06) compared with those in the first tertile. Higher GL values were linked to lower odds for mental disorders (OR: 0.66; 95% CI: 0.49, 0.90; P-trend = 0.009), depression (OR: 0.69; 95% CI: 0.51, 0.93; P-trend = 0.02), and psychological distress (OR: 0.67; 95% CI: 0.48, 0.92; P-trend = 0.01). Significant interactions were observed between GI and sex for depression (P = 0.01) and psychological distress (P = 0.046) in the crude model. In stratified analyses by sex, after control for potential confounders, a greater GI was linked to a higher odds of depression (OR: 1.52; 95% CI: 1.20, 1.94; P-trend = 0.001) and psychological distress (OR: 1.66; 95% CI: 1.28, 2.14; P-trend = 0.001) in women but not in men. Conclusion: Our findings support a direct link between the odds of depression and dietary GI but inverse associations between GL and mental disorders, depression, and psychological distress. This trial was registered at clinicaltrials.gov as NCT02362113.Am J Clin Nutr 2016;103:201-9.