Abstract Background Food-drug interactions (FDIs) are very common, but under-reported due to a lack of proper history or lack of knowledge and limited research. Our study highlights the knowledge gap among oncology patients treated with capecitabine regarding food-oral chemotherapy interactions. Method A cross-sectional study was conducted among 110 breast and colon cancer patients, purposively sampled from the chemotherapy outpatient clinic from June 2021 to December 2021. A structured questionnaire and interviews were used to collect data, we asked them about the information they had received from the doctor and the way they were taking the medicine. Data were analyzed using SPSS, and the p-value of p < 0.05 was considered significant. Results Regarding the sociodemographic and clinical data of participants, their ages widely ranged from 20-83 years old, and their mean age was 54.78±13.18. The majority of participants were females 81(73.6%), non-employed 86(78.2%), colon cancer 72(65.5%) and received ≤4 cycles 66 (60%). Still, there is poor awareness concerning FDI among oncology patients and most participants were unaware of the possible interactions of capecitabine with grapefruits, vitamins, herbs, and antioxidants, but the majority 92 (83.6%) were taking their medication correctly concerning meal recommendations and only 18(16.4% )were not taking capecitabine within 30 minutes of meals. The current study showed that patients’ knowledge was not associated with age, sex, education, marital status, or occupation. The main factors that affected knowledge in the current study were the cancer site and the number of treatment cycles, as colon cancer patients and those who have received four or fewer cycles had better doctor-patient communication. Conclusion There is a lack of awareness about interactions between oral chemotherapy and various nutrients and supplements among patients in the current study. Patient education and better doctor-patient communication are recommended to ensure optimal oral chemotherapy intake and patient safety.