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Ethnopharmacological Relevance: Bixa orellana L. is reported to have numerous applications in traditional medicine and pharmacological properties such as wound healing, analgesic, hemostatic, and antioxidant activities. Recently, the literature has shown scientific interest of its antimicrobial properties aiming the development of cost-effective phytotherapeutic agents. However, no literature are available in witch the antimicrobial and technological prospecting are summarized., Aim of Study: This study aimed to systematically review articles and patents related to the antimicrobial activity of B. orellana., Methods: The review followed the guidelines proposed by The Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Two reviewers performed a literature search up to November 2021 in eight databases: Medline (PubMed), Scopus, Scifinder, Web of Science, Cochrane, Embase, Scielo, and Biblioteca Virtual em Saúde. The following databases for the patent search were analyzed: United States Patent and Trademark Office (USPTO), Google Patents, National Institute of Industrial Property (INPI), World Intellectual Property Organization (WIPO), and Espacenet (European Patent Office, EPO). The grey literature was searched using the ProQuest Dissertations and Periódicos Capes Theses database. The methodological quality and risk of bias in the included studies were carried out using Review Manager (RevMan) 5.3.5., Results: After analyzing the 47 studies and five patents fulfilled all the criteria and were included in the present investigation. The evidence suggests that this herbal medicine is effective against several fungi, Gram-positive and Gram-negative bacteria, being more effective to Gram-negative bacteria. Regarding the risk of bias and methodological quality analysis, most studies a high risk of bias related to random sequence generation and allocation concealment., Conclusion: Up to now, the evidence in the literature suggests that the use of B. orellana preparations for antimicrobial preparations has some effectiveness. However, further research is needed using standard B. orellana preparations to determine their effectiveness as antimicrobial agents and expanding their application at an industrial level, in addition in vivo studies are needed for this confirmation., (Copyright © 2021 Elsevier B.V. All rights reserved.)