Sixty-one patients (22 patients with congenital adrenal hyperplasia [CAH] with a mean age of 14.86 years [range, 5–23], 20 patients with 5-α reductase deficiency type 2 [5α-RD-2] with a mean age of 19.5 years [range, 5–29], and 19 patients with complete androgen insensitivity syndrome [CAIS] with a mean age of 18.26 years [range, 5–28]) were evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia, the Structured Clinical Interview for DSM-IV Axis I, Axis II, and the Global Assessment Functioning Scale. All participants were female-assigned at birth. Ten patients (16.4%) transitioned to the male gender. Overall, 68% of patients had one or more lifetime Axis I disorders, including 63.6% of the CAH participants, 90% of 5α-RD-2 participants, and 52.6% of the CAIS participants. The most commonly observed were affective disorders (27.9%), gender identity disorder (27.9%), and anxiety (16.4%). Our study demonstrates that mental health of Iranian patients with DSD is at risk. This might be due to the fact that patients with DSD conditions are mostly treated medically and their mental health is often superficially addressed in developing countries such as Iran, at least in the past. We argue that it is important to pay attention to the mental health issues of patients with DSD and focus on specific issues, which may vary cross-culturally.