Objective: This study investigated the influence of psychosocial factors on medical students’ quality of life (QOL). Methods: A total of 408 medical students participated in this study. We collected data on participants’ sociodemographic details, symptoms of depression and Internet addiction, self-esteem, social support, and QOL. QOL was assessed using the World Health Organization Quality of Life-Abbreviated form, which has four domains (physical health, psychological health, social relationships, and environment). A stepwise multiple linear regression model was constructed to identify factors’ independent impact on QOL. Results: Higher levels of depression and Internet addiction were associated with lower scores in all domains of QOL, whereas higher levels of self-esteem and social support were associated with higher scores. Being in third-year versus first-year was associated with higher scores in the physical health and environment domains. Living alone or in dormitories, low or middle socioeconomic status, and insufficient or moderate pocket money were associated with lower scores in the environment domain. Additionally, female students displayed significantly lower scores for physical health, psychological health, and environment than male students, but not for social relationships. There were significant differences in certain domains of QOL due to sociodemographic factors. Conclusion This study demonstrates the psychosocial factors influencing medical students’ QOL. Educational strategies focusing on strengthening self-esteem and social support as well as preventing depression and Internet addiction may contribute to improving medical students’ QOL.