Background: Substance-Related Disorders are among the most common social problems caused by using legal and illegal substances. Therefore, this study aimed at determining the quality of life (QoL) and its related factors among women with substance use disorders referring to substance abuse treatment centers in Hamadan, west of Iran.Methods: This cross-sectional study was carried out on 120 Iranian female substance users recruited through the census sampling method in 2018. Data collection tools consisted of demographic characteristics and QoL assessment (SF-36). Data were analyzed using SPSS-16 via one-way analysis of variance (ANOVA) and chi-square tests.Results: The mean age of the participants was 33.2±12.1 years and the mean score of their total QoL was 35.35±13.5. The results of multiple linear regression analysis indicated that using methamphetamine (β=-6.62) was the predictor of QoL in women. Moreover, there was a significant association between QoL and age (p <0.001), educational level (p = 0.011), and age at first use (p <0.001).Conclusion: According to the results, the participants’ QoL was found to be at an unsatisfactory level. So, it is essential to implement educational help-seeking behavior for treatment and effectiveness educational, as well as holding mental health intervention, school-based substance abuse prevention, and harm reduction programs of substance use. This is especially important in adolescents, young, low-educated, early drug use, and methamphetamine user women, as it may increase the QoL