As part of the US FDA’s evaluation of potential regulatory frameworks for cannabidiol (CBD) and other cannabis-derived products, the agency has consistently raised concerns about the limited scientific information on CBD and need for further study. To assist in identifying knowledge gaps and inform future decision making, systematic mapping of the safety-related literature for CBD was performed. The systematic evidence map approach uses a structured process to describe the state of knowledge for a topic and provides a comprehensive synthesis of available data that can be queried for specific information. The systematic map for CBD was prepared using evidence-based methods, following an a priori protocol and the PECO (population, exposure, comparator, outcome) approach to develop research objectives. A broad and transparent systematic literature search was conducted in PubMed and Embase. Titles and abstracts were assessed and categorized in DistillerSR, and evidence tables and other visualizations prepared. The literature search yielded a total of >3,100 unique returns; of these, >2,200 articles (most published since 2010) were deemed relevant and included in the systemic map. Studies evaluating the beneficial properties and mechanistic pathways of CBD accounted for ~40% and ~20%, respectively. Regarding safety, the frequency of endpoints of interest assessed was as follows: pharmacokinetics > drug interactions > developmental and reproductive toxicity (DART) = general toxicity > immunomuodulatory effects > mutagenicity/genotoxicity = hepatotoxicity. Additional categorical information was assessed, including test material, test system, route of exposure, and adverse/beneficial findings. For example, studies reporting DART outcomes were conducted primarily in laboratory animals; few were conducted in vitro or in humans. While many studies reported adverse reproductive effects associated with CBD, the lack of a published guideline compliant reproductive toxicity study was identified as a data gap. This assessment provides a reliable summary of the state of the evidence for evaluating health risks following exposure to CBD. The mapping results will help identify knowledge gaps and future research needs, as well as support future systematic reviews and other safety assessments of human exposure to CBD.