Background: Chronic diseases are major causes of morbidity, disability, and death worldwide. In many cases, they are potentially preventable and treatable. Glaucoma is one of the leading causes of morbidity and blindness, the early recognition of which can help reduce the adverse outcomes of the disease. Health illiteracy among these patients and the absence of self-management of these diseases are barriers to effective management worldwide. Therefore, the present study aimed to calculate the level of health literacy and activity level of patients’ activation in self-management and to explore the link between them among patients with glaucoma in outpatient clinics. Material and methods: Convenience sampling of patients with glaucoma attending the outpatient ophthalmology clinics of a university hospital in Heraklion-Greece was performed. Convenience sampling was used to recruit 312 participants. Data were collected between November 2023 and May 2024. The Patient Activation Measure-13 (PAM-13) questionnaire, in its Greek version, was used to evaluate patients’ activation level in self-management, whereas the Greek version of the European Health Literacy Survey Questionnaire 16 (HLS-EU-16) was used to assess health literacy. Results: Participants were classified as level 1(disengaged & overwhelmed) level in self-management (= 40.7, SD: ±29.9) and a sufficient health literacy level (= 10.7, SD ±3.7). However, there was no statistically significant relationship between health literacy levels and patient activation in self-management (p=0.602). Conclusions: Glaucoma patients experience challenges with health literacy and self-management activation, though there is no significant relationship between these two parameters. Multifaceted interventions seem essential for enhancing patients’ activation. Further research involving larger sample sizes, multi-center studies, and interventional design is needed.