Background: Health literacy skills are critical since they influence how older adults recognize their health issues; manage their symptoms and engage in successful coping with their cancer. Purpose: This study aimed to evaluate the effect of health literacy intervention on self-efficacy and symptoms distress among older women with breast cancer undergoing chemotherapy. Design& Setting: This randomized control trial study was conducted during 2022-2023 in the oncology day clinic at Zagazig University Hospitals. Sample: The study sample composed of 100 older breast cancer patients undergoing chemotherapy, randomly assigned into two groups. The study group (n=50) received six sessions every two weeks and the control group (n=50) received no intervention. Tools: Four tools were used; interview questionnaire, All Aspects of Health Literacy Scale, the Cancer Behavior Inventory-Brief Version, and the Memorial Symptom Assessment Scale Short Form. Data Analysis: Chi-square test, independent samples t-test, paired t-test, Pearson correlation, and linear regressions were used for data analysis. Results: The study findings showed statistically significant improvements in the study group’s health literacy, self-efficacy, and lowering symptoms distress compared to the control group (p < .01). Also, total health literacy score of the study group after the intervention positively correlated to self-efficacy score (r = 0.501) and symptom distress score was negatively correlated to total health literacy score (r = -0.478) and self-efficacy score (r = -0.562). Conclusion: Health literacy intervention was effective and could be used to enhance patients’ health literacy and self-efficacy, and decrease symptoms distress in older women with breast cancer undergoing chemotherapy.