Across the decades, malaria disease has been a public health problem. The use of natural products to treat malaria saved many lives over the centuries, but the parasite resistance against all the medicines available on the market has made it difficult. In this context, exploring new natural treatments from biodiverse ecosystems, such as oceans, holds promise. Marine sponges have been used in different ways to treat diseases, their secondary metabolites and endoperoxides showed antiplasmodial activity in different assays. With that in mind, the species of marine sponge Tedania ignis, was evaluated against sensitive and resistant laboratory P. falciparum strains and presented potential antimalarial activity. Moreover, the speed of action of the extract of T. ignis was assessed demonstrating a fast-active profile. Regarding cellular cytotoxicity assays, the compound under investigation did not exhibit cytotoxic effects on two cell lines: HepG2, derived from human hepatoma, and HEK 293 (Human Embryonic Kidney). The active extract of T. ignis was investigated using UHPLC-HRMS and for data analyses was used Global Natural Products Social Molecular Networking (GNPS). Eight metabolites were dereplicated belonging to classes of alkamides, terpenes, nucleobases, alkaloid, and benzoic acid ester. Among the compounds assigned, dibutyl phthalate is highlighted for its known antimalarial potential, which may contribute to the bioactivity of T. ignis extract revealed in this work.