Background and Objectives: Skin problems are a widespread issue that affects people in both developing and wealthy countries, posing significant public health concerns. These disorders can profoundly impact individuals’ social and psychological well-being. In this study, we aimed to determine the prevalence of the most common skin diseases in the Jazan region of southwestern Saudi Arabia and investigate their impact on patients’ quality of life and psychological and social well-being. Materials and Methods: An observational cross-sectional survey conducted among a random sample of 940 adults ≥ 18 years in the Jazan region, Saudi Arabia. Four standardized questionnaires were used for data collection: Patient Health Questionnaire (PHQ-9), a five-dimension questionnaire (EQ-5D), Rosenberg Self-Esteem Scale, and Loneliness Scale (ULS-8). Results: The most prevalent skin conditions involved hair loss, which was reported by (61.1%) of the study population. These disorders significantly affected a higher percentage of females (71.9%) compared to males (46.3%) (p < 0.001). Melasma was more common in females (14.1%) than in males (4.3%) p < 0.001. The lowest prevalence was found for urticaria. Those with acne and hair loss reported higher mean scores on the PHQ-9 Scale than the group without these conditions (p < 0.05 for all). Patients with alopecia, acne, and melasma also reported significantly lower self-esteem scores compared to those without these skin conditions (p < 0.05 for all). Regarding the activity domain of QoL, participants with skin conditions reported no problems doing usual activities, compared to those without skin problems (p < 0.001). Conclusions: In conclusion, research revealed that the most prevalent skin condition was hair loss. Further, an association was found between skin diseases and the mental and social well-being of those affected, resulting in a negative impact on their quality of life. The results call for improving the condition of patients with skin diseases, improving their quality of life, and providing appropriate interventions.