Introduction: Health literacy, the ability to access, understand, evaluate, and apply relevant information, plays a key role in making informed decisions about health. Promoting health literacy from early childhood may help reduce disparities in oral health. This study aimed to examine the relationship between health literacy, perceived oral health, and oral health-related quality of life among adolescents in San Fabián, Chile. Material and Methods: A cross-sectional, correlational study was conducted involving 122 adolescents aged 15 to 19 years, selected through stratified sampling. Health literacy and oral health–related quality of life were assessed using the HLS-EU-Q16 and OHIP-14 questionnaires, respectively. Perceived oral health was measured using a single validated question. The strength of the relationships between variables was evaluated through correlation analysis. Results: A total of 62.3% of adolescents showed inadequate and problematic levels of health literacy. Despite reporting good brushing habits, gaps were identified in flossing and regular dental visits. Health literacy was positively associated with perceived oral health and oral health-related quality of life. Conclusions: This study highlighted the importance of improving health literacy among adolescents in a rural area. It is suggested that health promotion efforts and dental services be tailored to the health literacy levels of Chilean youth to enhance their oral health and overall quality of life. © 2025 Elsevier B.V., All rights reserved.