The differences between females and males in personality disorders and reinforcement sensitivity systems are stated in many studies. However, the underlying reasons for these differences are not clear, and also there are limited studies about the moderating role of gender via emotion regulation. In this respect, in this study it was aimed to examine the moderated mediation role of emotion regulation and gender in the relationships between reinforcement sensitivity systems and personality disorders. In the study, 427 (28.52±11.05) participants, 262 females (61.4%) and 165 males (38.6%) between the ages of 18-66 were included. Coolidge Axis II Inventory Plus Turkish-Short Form, Reinforcement Sensitivity Questionnaire and Difficulties in Emotion Regulation-Brief Form were used. Pearson Product Moments Correlation coefficient method, Fisher's Z test, independent samples t-test and Model 59 in the "PROCESS Macro v.3.5" program was applied for statistical analysis. It was found that Personality Disorder (PD), Borderline PD, Histrionic PD, Narcissistic PD, Avoidant PD, Dependent PD, BIS, Flight, Freeze and Difficulties in Emotion Regulation Scale scores were significantly higher in women; Antisocial PD scores were significantly higher in males. It was found that emotion regulation and gender have moderated mediation role in the models that include Schizoid PD, Dependent PD, Borderline PD, Antisocial PD, Obsessive Compulsive PD, Histrionic PD and Narcissistic PD. The findings show that men and women are affected in different ways from the difficulties in emotion regulation and reinforcement sensitivity systems in regards to personality disorders.