INTRODUCTIONOrphan diseases (OD) are rare but collectively common, presenting challenges such as late diagnoses, disease progression, and limited therapeutic options. Recently, artificial intelligence (AI) has gained interest in the research of these diseases.OBJECTIVETo synthesize the available evidence on the use of AI in the comprehensive approach to orphan diseases.METHODSAn exploratory systematic review of the Scoping Review type was conducted in PubMed, Bireme, and Scopus from 2019 to 2024.RESULTSfifty-six articles were identified, with 21.4% being experimental studies; 28 documents did not specify an OD, 8 documents focused primarily on genetic diseases; 53.57% focused on diagnosis, and 36 different algorithms were identified.CONCLUSIONSThe information found shows the development of AI algorithms in different clinical settings, confirming the potential benefits in diagnosis times, therapeutic options, and greater awareness among health professionals.