Acne is a common skin condition affecting both adolescents and adults, and it can profoundly impact patients’ quality of life and mental well-being. This prospective cross-sectional study aims to explore the differences in psychosocial aspects between male and female acne patients in Poland. A total of 104 consecutive acne patients were included in this study. Clinical severity, patients’ quality of life, stigmatization levels, and psychiatric disturbances were evaluated using the following instruments: Investigator Global Assessment (IGA), Dermatology Life Quality Index (DLQI), Cardiff Acne Disability Index (CADI), 6-Item Stigmatization Scale (6-ISS), and Hospital Anxiety and Depression Scale (HADS). This study found that female patients exhibited significantly less severe acne and experienced significantly decreased quality of life and increased levels of stigmatization. Furthermore, anxiety levels among female patients exceeded those observed in their male counterparts. Notably, no disparities in the severity of depression were observed between the two gender groups. Correlations were discerned among all psychosocial parameters in the entire study cohort and in the female subgroup, while such correlations were not uniformly observed among male participants. This study underscores the importance of considering psychosocial aspects and implementing routine measurements in the management of acne to improve patients’ well-being.