BACKGROUND: The aim of this study was to assess the knowledge, attitude, and practice of complementary and alternative medicine (CAM) and its impact on antiepileptic drug (AED) adherence among patients with epilepsy. METHODS: A cross-sectional study was carried out on 100 epilepsy patients, aged 18 years or older that did not have any physical or psychiatric illness. A patient-administered questionnaire was used to assess their knowledge, attitude towards, practice, and perceived effectiveness (KAPP) of CAM. Established adherence assessment tools were used to determine patient medication adherence. RESULTS: The prevalence of CAM usage was found to be at 58%. CAM was used more frequently by males (n = 32, 60.4%) than by females (n = 26, 55.3%; p = 0.609). The most commonly used CAM included vitamins and minerals (36%), ginseng (16%), antioxidants (15%), and acupuncture (12%). A significant number of patients had low knowledge of (59%) and a positive attitude (54%) toward complementary and alternative medicine. Main reasons for using CAM were a lower price, better availability, and inadequate seizure control by AEDs. About 43% of the patients who used CAM informed their doctor. Prevalence of non-adherence to AED therapy was found to be 68%. A significant association was found between non-adherence and CAM usage (p < 0.01). CONCLUSION: A high prevalence of CAM usage and non-adherence to AEDs among epilepsy patients was identified. CAM usage was associated with a non-adherence to AED therapy. This study highlights the need to explore CAM usage with patients before making clinical decisions to achieve the best outcomes from AED therapy.