Abstract The phycocyanin (PC) in the crude extract is one of the main active compounds that has significant anti-inflammatory properties and the potential to treat gingival inflammation, the common oral disease. This work reports the preparation and characterization of chitosan/pluronic F-127 hydrogels entrapping the crude extracts of PC from Arthrospira platensis (C005H and C005L) as a local drug delivery system aiming to prolong PC release for the treatment of gingivitis. The results showed that the total phenolic content (TPC) values of the crude extracts were in the range of 2 to 5 μg GAE/100g and presented above 85% inhibition in the protein denaturation test and over 65% using a lipoxygenase (LOX) inhibition test. The hydrogels incorporating the crude extracts from C005H and C005L were perfectly prepared via the electrostatic interaction between chitosan and pluronic F-127 with very high encapsulation efficiency. The crude extracts of PC C005H and C005L were released over 70% from the loaded hydrogel within 6 hours under artificial saliva conditions. The anti-inflammatory activity of the released supernatant from the hydrogels after 6 hours was around 32-47% by LOX inhibition. The hydrogel vehicles and loaded-hydrogels did not show any cytotoxic effects against mouse fibroblast cell lines (L929) and human gingival fibroblast cells. Our current work shows that the crude extract PC-loaded chitosan/pluronic F-127 hydrogel is biocompatibility with human cells and shows prolonged crude extract release properties, suggesting it as an alternative treatment approach for gingivitis. Keywords: Phycocyanin, Gingivitis, Hydrogel, Chitosan, Pluronic F-127