Microorganisms play a significant role in biofouling and biocorrosion within the maritime industry. Addressing these challenges requires an innovative and integrated approach utilizing marine natural products with beneficial properties. A comprehensive screening of 173 non-toxic EtOAc and H₂O extracts derived from diverse marine organisms collected in Indonesian waters was conducted using a robust panel of assays. These included antimicrobial tests and classical biosurfactant assays (drop collapse and oil displacement), as well as anti-quorum-sensing (QS) and anti-biofilm assays. These screening efforts identified five active extracts with promising activities. Among these, EtOAc extracts of the marine tunicate Sigilina cf. signifera (0159-22e) and the marine sponge Lamellodysidea herbacea (0194-24c) demonstrated significant anti-biofouling activity against Perna indica and anti-biocorrosion performance (mpy 10.70 ± 0.70 for S. cf. signifera; 7.87 ± 0.86 for L. herbacea; 13.60 ± 1.70 for positive control Tetracorr CI-2915). Further chemical analyses of the active extracts, including LC-HR-MS/MS, MS-based molecular networking, and chemoinformatics, revealed the presence of both known and new bioactive compounds. These included tambjamines and polybrominated diphenyl ethers (PBDEs), which are likely contributors to the observed bioactivities. Subsequent investigations uncovered new anti-QS and anti-biofilm properties in synthetic and natural PBDEs 1–12 previously derived from L. herbacea. Among these, 8 exhibited the most potent anti-QS activity, with an IC₅₀ value of 15 µM, while 4 significantly reduced biofilm formation at a concentration of 1 µM. This study highlights the potential of marine-derived compounds in addressing biofouling and biocorrosion challenges in a sustainable and effective manner.