BackgroundThe use of herbal medicine (HM) as a self-management practice for treating various diseases has gained popularity worldwide. Consumers co-administer herbal products with conventional medicine without the knowledge of possible herb-drug interaction (HDI).AimThis study aimed to assess patients’ perception and use of HM and their knowledge of HDI.SettingParticipants attending primary health care (PHC) clinics in three provinces (Gauteng, Mpumalanga and Free State), South Africa, were recruited.MethodsFocus group discussions comprising a total of thirty (N= 30) participants were conducted using a semi-structured interview guide. Discussions were audio-recorded and then transcribed verbatim. Data were analysed using thematic content analysis.ResultsReasons for using HM, sources of information on HM, co-administration of HM and prescribed medicine, disclosure of the use of HM, PHC nurses’ attitudes and not having time to engage were frequently discussed. Respondents’ lack of knowledge and perceptions about HDI and their dissatisfaction with prescribed medicine because of experienced side effects were also discussed.ConclusionBecause of the lack of discussions and non-disclosure about HM in PHC clinics, patients are at risk of experiencing HDIs. Primary health care providers should regularly enquire about HM use on every patient, to identify and prevent HDIs. The lack of knowledge about HDIs by patients further compromises the safety of HM.ContributionThe results highlighted the lack of knowledge of HDI by patients thus assisting the healthcare stakeholders in South Africa to implement measures to educate patients attending PHC clinics.