<![CDATA[Indonesia possesses high biodiversity with significant potential as a source of natural immunomodulators, particularly from endemic flora of Kalimantan such as Eurycoma longifolia, Stenochlaena palustris, and Piper crocatum, which are rich in bioactive secondary metabolites. However, their clinical application remains limited due to poor bioavailability and physicochemical instability. This scoping review was conducted following the methodology of the Joanna Briggs Institute using the Population, Concept, Context (PCC) framework. Literature searches were systematically performed in PubMed, Scopus, Web of Science, and ScienceDirect, followed by descriptive analysis to map formulation strategies, immunomodulatory mechanisms, and translational challenges. The findings indicate that pharmaceutical nanotechnology, including nanoemulsions, self-nanoemulsifying drug delivery systems (SNEDDS), and nanoparticles, significantly enhances solubility, stability, and delivery efficiency of bioactive compounds. At the cellular and molecular levels, immunomodulatory effects involve enhanced phagocytic activity, regulation of cytokines such as TNF-α, IL-6, and IL-10, and modulation of signaling pathways including NF-κB and MAPK. Nevertheless, clinical translation remains challenged by safety concerns, formulation stability, high development costs, and regulatory requirements. Overall, pharmaceutical nanotechnology offers a promising approach to optimize natural product-based immunomodulators; however, further standardization, robust clinical evidence, and multidisciplinary collaboration are essential to support successful clinical implementation.]]>
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