Previous investigations have mostly studied an individual methyl donor nutrient in relation to psychological disorders and the findings were inconsistent. We investigated the association of methyl donor micronutrients (folate, B6, B12, choline, betaine and methionine) with psychological disorders in Iranian adults. In this cross-sectional study, dietary intakes of 3299 adults were collected using a validated food frequency questionnaire. Methyl donor micronutrient score (MDMS) was calculated based on energy-adjusted deciles of each nutrient. Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire (GHQ), validated for Iranians, have been applied to assess depression, anxiety and psychological distress. Participants had a mean age of 36·3 ± 7·9 years, of whom 58·5 % were women. After considering potential confounders, adults in the top quartile of MDMS, compared to the bottom one, had decreased odds of anxiety (OR: 0·53, 95 % CI: 0·37, 0·75), depression (OR: 0·75, 95 % CI: 0·58, 0·97) and psychological distress (OR: 0·61, 95 % CI: 0·46, 0·80). Among women, the top quartile of MDMS was protectively associated with anxiety (OR: 0·60, 95 % CI: 0·40, 0·90), depression (OR: 0·68, 95 % CI: 0·50, 0·93) and psychological distress (OR: 0·53, 95 % CI: 0·38, 0·74). Overweight and obese subjects in the highest quartile of MDMS had a 67 %, 35 % and 53 % lower odds of anxiety (95 % CI: 0·20, 0·56), depression (95 % CI: 0·44, 0·94) and psychological distress (95 % CI: 0·31, 0·70), respectively. We found that high consumption of methyl donor micronutrients was related to a reduced odds of psychological disorders, especially in women and overweight or obese individuals.