Various studies have shown that influencing factors such as gender, race, and socio-economic status could significantly impact adolescents’ health literacy in South Africa. The adolescent stage is crucial for acquiring and developing health-promoting knowledge and behaviors. Therefore, this study aimed to analyze the gender-specific determinants that prevent adolescents from accessing, understanding, and utilizing health-related information and services through an intersectionality theoretical lens. This study used content analysis of secondary data from 2010 until 2023 from electronic databases such as SciELO, Google Scholar, the Directory of Open Access Journals, Scopus, and governmental reports. From the initial 102 articles and documents obtained from the search process, a total of 26 papers were included in this study. The results indicated that gender roles, cultural norms, heteronormativity, gender-based violence, and associated stigmatization are gender-specific barriers to adolescents’ health literacy in South Africa. Based on the study findings, I argue that multi-stakeholder engagement is needed to address the identified barriers and collaboratively develop and implement a gender-responsive health literacy programme that promotes equitable and non-judgmental access for young people to health information and services in South Africa.