Background: Myocardial infarction is one of the deadly diseases characterized by the presence of blood clot inhibiting the circulation of blood to the heart, caused by ecto-ATPase. Sponges Clathria vulpina and Stylissa carteri have bioactive compounds that can be an alternative in inhibiting ecto-ATPase. This research aimed to find the potential of bioactive compounds from Indonesian Clathria vulpina and Stylissa carteri in acting as inhibitory agents for ecto-ATPase. Methods: The bioactive compounds were extracted by maceration using methanol solvent. The bioactive compound from the sponge extracts were profiled using GC-MS. Hemolytic and hemagglutination activities of Clathria vulpina and Stylissa carteri extracts were also done. Results: Bioactive compound profiles from Clathria vulpina extract were found as derivatives of palmitic acid, oleic acid, stearic acid, arachidonic acid, and DHA. Meanwhile, bioactive compound profiles from Stylissa carteri extracts as derivatives fatty acids, alcohol and steroids. Both Clathria vulpina and Stylissa carteri extracts had hemolytic activities, but did not have hemagglutination activity. Molecular docking analysis showed that Clathria vulpina bioactive compounds cannot bind ecto-ATPase better than control positive, and Stylissa carteri bioactive compounds can bind ecto-ATPase better than positive control. Conclusion: Bioactive substances from Indonesian sponges Clathria vulpina and Stylissa carteri were known as ecto-ATPase inhibitors. These findings suggest that Stylissa carteri's bioactive substances may be ecto-ATPase inhibitors and should be further studied for myocardial infarction treatment.