In this opinion, EFSA's Scientific Committee provides guidance on the scientific data needed to carry out a safety assessments of a botanical or a botanical preparation. It also proposes a two‐tiered scientific approach for the safety assessment depending on the available knowledge on a given botanical and the substance(s) it contains. The guidance also provides a set of criteria to help prioritise the safety assessment of botanical ingredients which are in use. EFSA has also compiled the available information on a large number of botanicals which have been reported to contain substances that may be of health concern when used in food or food supplements. The resulting compendium, which will be regularly updated, should be considered as part of this guidance document and is intended to assist manufacturers and food safety authorities by highlighting possible safety issues which may require further consideration.