Background Over-the-counter medicines must be supplied with appropriate, user-friendly medicine information to satisfactorily support consumer self-management and safe use. Product labels and written medicine information leaflets are highly accessible over-the-counter medicine information sources for consumers. Factors such as comprehensibility and design underpin the usefulness of over-the-counter labels and leaflets and should be further examined to better inform future optimisation strategies. Aim of the review To undertake an in-depth exploration of studies that have evaluated design and/or comprehensibility of over-the-counter labels and written medicine information leaflets Methods Database searches were performed using Medline, Embase, International Pharmaceutical Abstracts and PubMed. Studies exploring over-the-counter medicine label and/or leaflet comprehensibility and/or design were identified. Additional author and reference list searches were performed to identify studies which met the inclusion criteria and key terms. Results A total of 35 studies were included in the review, which explored OTC medicine information design and/or comprehensibility via researcher evaluation alone (n = 8) or with consumers (n = 27). Researcher-determined over-the-counter written medicine information leaflet readability (n = 4) has highlighted suboptimal readability, with few studies evaluating over-the-counter leaflet performance using the gold standard method of ` user testing' with consumers (n = 2). Variable over-the-counter label comprehensibility was identified in consumer studies, ranging from satisfactory understanding to considerable misunderstanding. The review findings indicate that consumer outcomes were influenced by information design, where implementation of good design principles generally improved over-the-counter label and leaflet performance. Significant diversity existed in study design aspects such as sampling frames, sample sizes and tools used to evaluate over-the-counter medicine information, which hindered the ability to adequately compare various study aspects and findings. Conclusion A wide spectrum of consumer understanding of over-the-counter medicine labels is evident in the literature, with limited studies examining over-the-counter written medicine information leaflet comprehensibility with consumers. The application of good information design principles in over-the-counter labels and leaflets contribute to improved performance. Well-designed consumer studies are needed to ascertain and optimise overthe- counter label and leaflet performance.