The personality trait of social introversion refers to the individual inclination toward the inner/outer world. Moreover, adolescents who experience Gender Dysphoria (GD) can be involved in relationship conflicts with family, peers, and friends and experience stigmatization and rejection from society. This leads higher distress in females which are more sensitive to this kind of feelings. This leads in them frequently developing a negative sense of well-being and low self-esteem which increases their risk of internalizing symptoms. So, the aims of this study were: (1) to investigate the presence of significant differences in Social Introversion (SI) dimensions between an assigned-female at birth (AFAB) GD group and a cisgender female group both diagnosed with a depressive disorder, (2) to verify whether the two clinical groups may be characterized by different profiles of internalizing symptoms, (3) to investigate if the SI dimensions could promote the internalizing symptomatology. Our results confirmed the presence of significantly higher score in GD sample for MMPI-SI scale and subscales and showed no significant difference in depressive profiles. Lastly, SI could promote internalizing symptomatology in AFAB underlying a link between SI and depression in this condition which should be further investigated.