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Emerging evidence highlights noncoding RNAs (ncRNAs) as critical regulators of host\u2013parasite interactions, offering novel opportunities for diagnosis, prognosis, and targeted therapy. However, most of these findings are derived from in vitro experiments and preclinical models with limited validation in clinical settings. This review comprehensively examines the roles of microRNAs (miRNAs), small interfering RNAs (siRNAs), and long noncoding RNAs (lncRNAs) in the diagnosis and treatment of major parasitic diseases, including malaria, leishmaniasis, trypanosomiasis, Chagas disease, helminthic infections, cryptosporidiosis, and scabies. Distinct miRNA expression profiles are associated with disease presence, severity, and clinical outcomes, positioning them as promising noninvasive biomarkers detectable in body fluids. Specific miRNAs such as miR\u2010223, miR\u2010155, miR\u2010145, and miR\u20103158 modulate immune responses, inflammation, and parasite survival across multiple infections. Beyond diagnostics, miRNAs actively participate in disease pathogenesis and host defense, enabling therapeutic modulation of immune pathways. siRNA\u2010based approaches further demonstrate therapeutic potential through RNA interference\u2013mediated silencing of essential parasite genes, successfully impairing parasite growth, viability, and development in diseases such as cystic echinococcosis, cryptosporidiosis, and scabies. Additionally, lncRNAs have emerged as key regulators of innate and adaptive immunity, influencing cytokine signaling, macrophage differentiation, and inflammatory pathways while serving as novel biomarkers for parasitic cardiomyopathies and protozoan infections. Despite promising advances, the clinical translation of ncRNA\u2010based diagnostics and therapeutics faces significant challenges, including delivery efficiency, stability, specificity, off\u2010target effects, and ethical considerations. Continued research, improved delivery platforms, and well\u2010designed clinical trials are essential to harness the full potential of ncRNAs. Therefore, while ncRNA\u2010based strategies represent a promising direction for future research, their application in parasitic disease diagnosis and therapy remains largely at an experimental level. Continued investigation of ncRNA\u2010based methods is required to address current limitations and enable safe and effective clinical translation.<\/jats:p>","DOI":"10.1155\/japr\/4071834","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:09:44Z","timestamp":1781082584000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling the Silent Regulators: Noncoding RNAs in Parasitic Disease Diagnosis and Therapy"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1575-0522","authenticated-orcid":false,"given":"Neyon","family":"Loku Gamage","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2016-2803","authenticated-orcid":false,"given":"Koshila","family":"Ranasinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_2_19_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl046"},{"key":"e_1_2_19_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.312"},{"key":"e_1_2_19_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-42059-2_1"},{"key":"e_1_2_19_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-014-0088-0"},{"key":"e_1_2_19_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-748-8_3"},{"key":"e_1_2_19_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.01076.x"},{"key":"e_1_2_19_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2024.1388476"},{"key":"e_1_2_19_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-008-9136-7"},{"key":"e_1_2_19_9_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2183803"},{"key":"e_1_2_19_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10142-016-0524-x"},{"key":"e_1_2_19_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-051410-092902"},{"key":"e_1_2_19_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.10.022"},{"key":"e_1_2_19_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07672"},{"key":"e_1_2_19_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00315-9"},{"key":"e_1_2_19_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0017-y"},{"key":"e_1_2_19_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(04)00045-5"},{"key":"e_1_2_19_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2015.10"},{"key":"e_1_2_19_18_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075013"},{"key":"e_1_2_19_19_2","doi-asserted-by":"publisher","DOI":"10.1017\/s0031182019001689"},{"key":"e_1_2_19_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2012.00048"},{"key":"e_1_2_19_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.f.209"},{"key":"e_1_2_19_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/hdy.2011.104"},{"key":"e_1_2_19_23_2","doi-asserted-by":"crossref","unstructured":"EtheridgeA. 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