Background: Health literacy is a new concept in health promotion services that has reflections on the outcomes of health education and communication activities. Health literacy provides skills that enable individuals to understand, share personal and health information with providers, navigate the healthcare system, engage in self-care, and adopt health-promoting behaviors. However, In Saudi Arabia, limited researches have been conducted in the nursing field to assess nurses’ knowledge and perception of health literacy. This study aimed to assess the nurses’ current knowledge and perception about the impact of health literacy on patients and their practice. Methodology: A descriptive survey design was used in this study. The sample consisted of 679 nurses who worked in a tertiary care setting. The data was collected using a self- reported questionnaire. Result: The study findings revealed that most of the nurses have moderate knowledge about health literacy, and the majority of participants perceived a limited impact of health literacy on patients care. Recommendation: It is important for health care organizations to have specialized tools that can effectively measure health literacy levels; there is an urgent need to design professional programs for healthcare professionals that enable them to improve their level of health literacy and organizations need to ensure the effective implementation of health literacy programs.