Introduction: Immunomodulator are chemical compounds that can improve the body’s defense mechanisms both specific and non-specific, and non-specific induction of both cellular and humoral defense mechanisms. Objectives: The objectives of this study were to investigate immunomodulator activity and to identify the chemical constituents of active fractions from star fish Acanthaster planci, based on bioassay guided isolation. Materials and Methods: A. planci was collected from Ternate Island, North Moluccas, extracted with distilled methanol, partitioned with gradient chloroform-hexane-water and fractionated in column chromatography using silica gel and gradient hexane-ethyl acetate. Profiling chemical constituent was done by thin layer chromatograpahy and GC-MS. The immunomodulator activity was measured based on percentage of phagocytic capacity (PC) and phagocytic index (PI). Results: The result showed that 3 partition fractions exhibited immunomodulator activity. Data analysis exhibited that the best fraction was hexane fraction, and the best dosesmost effective doses of PC and PI were at 0.5 mg/kg body weight (BW) and 0.7 mg/kg BW, respectively. Data analysis of the 3 hexane fractions exhibited that the best fraction was fraction 3 and the best doses of PC was at 0.5 mg/kg BW and that of PI was at 0.7 mg/kg BW. Metabolites analysis using GC-MS yielded a number of chemical constituents of fraction 2 dan fraction 3 that dominated by unsaturated fatty acid. The study concluded that star fish A. planci from Ternate Island has a potential source of immunomodulator.