The aim of the study was to understand healthcare professionals, pharmacists, and patients perspectives and experiences on clinical practice of herb-drug interactions (HDIs). A systematic review of qualitative studies was conduct. 10 electronic databases were searched from inception through September 2023. Qualitative studies, mixed-method studies, and unstructured or semi-structured cross-sectional surveys focused on healthcare professionals, pharmacists and patients' perspectives, attitudes, clinical practice behaviors, and information needs regarding HDI were included. Thematic synthesis employed Nvivo 12 software. Of 6655 studies identified, 1267 full-text articles were retrieved. Of these, 18 studies conducted in 11 countries/regions were eligible for inclusion, involving 1273 patients, 302 healthcare professionals, and 230 pharmacists. Five over-arching explanatory themes were identified: perspectives, attitudes, practices, experiences, expectations, and information needs. Complementary and alternative (CAM) physicians, pharmacists, and general practitioners were considered by patients to possess the ability or responsibility to assess potential HDIs. Pharmacists yet encountered difficulties due to conflicting information sources and inadequate training. Healthcare professionals, including pharmacists, usually only assessed HDIs when they were deemed to cause serious adverse effects. Regarding expectations and information needs, patients were particularly concerned about the risk of adverse HDIs, the severity of HDIs, and the appropriate intervals between drug doses. They would like to receive relevant HDI alerts. Results suggest that government, policy makers, healthcare professionals, and the education system should give attention to HDIs and improve health professional-patient communication. Further research should also be conducted on the understanding and practices of CAM practitioners in China. Trial Registration: CRD42022324777 (https://www.crd.york.ac.uk/PROSPERO/#recordDetails).
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