BACKGROUND The use of herbal medicines (HMs) is increasing, which raises concerns of herb-drug interactions (HDIs). This questionnaire-based study aimed to evaluate knowledge of HMs and HDIs in 147 undergraduate nursing students in Riyadh, Saudi Arabia, between March 2022 to June 2022. MATERIAL AND METHODS An online cross-sectional study was conducted among 147 nursing undergraduates at King Saud University, Riyadh, Saudi Arabia from March 2022 to June 2022, using a self-administered 24-item questionnaire. The convenience sampling method was used to evaluate the knowledge of HMs and interactions of anticoagulants, anti-inflammatory drugs, antibiotics, and antiplatelet drugs with herbs like ginkgo biloba, St. John's wort, garlic, ginger, green tea, and chamomile tea. RESULTS The findings of this study reported that 74.8% of the undergraduates used HMs. With regard to HDIs, 20.4% of nursing undergraduates identified the interaction between gingko biloba and drugs like ibuprofen and warfarin, while 13.6% identified interactions between drugs like warfarin with green tea, ginger, and chamomile tea. Regarding general knowledge, 59% of the students (n=84) reported good knowledge of HMs. Previous history of HM use significantly affected the mean HM knowledge score (t=4.635; P=0.0001). CONCLUSIONS To summarize, Saudi nursing students showed a lack of understanding and knowledge of HDIs. Ability to identify specific HDIs, like ginkgo biloba interactions with warfarin and ibuprofen, and warfarin interactions with green tea and ginger, was limited. There is a need to introduce HM and HDI courses in the academic curriculum.