Polysaccharides from various cyanobacterial species have attracted attention for their potential health benefits. In this study, polysaccharide extracts from a freshwater Nostoc sp. were explored for their potential in immunomodulation relevant to skincare, and particularly wound care. Nostoc sp. polysaccharides (NSPs) were tested in various cellular and molecular assays using RAW264.7 macrophages and skin cell lines (HDF, HaCaT). Polysaccharides from the Nostoc sp. outer layer (OL) and inner fluid (IF) significantly enhanced cell proliferation and migration of HDF. HaCaT scratch-wound healing improved with certain polysaccharide extracts. Inner fluid fractions IF-2B and IF-3B polysaccharides demonstrated anti-inflammatory effects in RAW264.7 cells, while IF-1B reduced TNF-α and IL-8 expression in HaCaT cells. TNF-α, though not promoting cell proliferation, positively impacted phagocytosis and NO production. NSPs exhibited weak anticoagulation properties, and fraction IF-1B with monomer composition (Ara/3.0: Glc/23.7: Man/20.3: GlcA/28.0) accelerated wound healing; importantly, OL-1B along with all of the IF cold and hot-extracted fractions were non-cytotoxic, suggesting significant potential for developing skin therapeutics, including pharmaceutical and cosmetic products, based on active compounds from Nostoc sp. The study underscores the underexplored potential of Nostoc sp. extracts in skincare and highlights the potential benefits of these bioactive components for therapeutic applications.