Introduction Several tools for the assessment of sexuality-related distress are now available. The Female Sexual Distress Scale (FSDS) and its revised version (FSDS-R) are extensively validated and among the most widely used tools to measure sexually related personal distress. Aim The aim of the study was to determine the psychometric properties of the Iranian version of the FSDS-R in a population sample of Iranian women. Methods A total of 2,400 married and potentially sexually active women were recruited and categorized into three groups including (i) a healthy control group; (ii) a group of women with hypoactive sexual desire disorder (HSDD); and (iii) a group of women suffering from other female sexual dysfunction (FSD). Participants were asked to complete a set of questionnaires including the Iranian version of the Female Sexual Function Index (FSFI-IV), the FSDS-R, and the Hospital Anxiety and Depression Scale. Main Outcome Measures Sexuality-related distress and FSD as assessed by the Iranian version of the FSDS-R and the FSFI-IV are the main outcome measures. Results Internal consistencies and test–retest reliability of the FSDS-R across the three assessments points for the three groups were >0.70. The FSDS-R correlated significantly with anxiety, depression, and the FSFI total score. Significant differences in the FSDS-R scores were found between healthy women, women with HSDD, and women with other types of FSD. Factor analysis of the FSDS-R yielded a single-factor model with an acceptable fit. Conclusions The Persian version of the FSDS-R is a valid and reliable instrument for the assessment of sexuality-related distress in Iranian women and can be used to screen patients with HSDD.