Acne vulgaris usually affects the dermal layer of the skin and is revealed frequently in young adulthood and adolescence. It has serious psychosocial comorbidities. We conducted the present systematic review and meta-analysis to elucidate the association of acne vulgaris with psychiatric comorbidities and quality of life as well as the brain-derived neurotrophic factor (BDNF) level. A systematic review and meta-analysis of the published articles were carried out following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We investigated diverse databases: Web of Science, PubMed, the Cochrane Library, Embase, PsycINFO, and CINAHL to search for articles reporting the prevalence of psychosocial comorbidities among patients with acne vulgaris from database inception through June 2022. The outcomes were depression, anxiety, symptom checklist-90-R (SCL-90-R), quality of life, self-esteem, stress, loneliness, and BDNF concentrations. Of 3647 articles identified, 23 met the inclusion criteria. Patients with acne vulgaris have a significantly higher level of anxiety, depression, and stress (P<0.05). Yet, the reported findings of the SCL-90-R, self-esteem, loneliness, and BDNF scores among patients suffering from acne vulgaris were variable and did not differ significantly compared to healthy participants (P>0.05), hampering any conclusive findings on absolute prevalence. Subgroup analysis and comparison showed that heterogeneity between studies was likely due to factors, including country, study design, and assessment tools. This comprehensive review and meta-analysis revealed that anxiety, depression, and stress are significantly more frequent among patients suffering from acne vulgaris. These findings confirm that acne vulgaris has both psychiatric and medical characteristics and requires a multidisciplinary approach.