Red Sea organisms represent key and genuine resources for biologically active metabolites. To provide preliminary clues about the biological activities of some Red Sea invertebrates, the soft coral Sarcophyton convolutum and the crab Charybdis natator were obtained. The whole amount of the coral and the shell part of the crab were subjected to extraction to obtain bioactive metabolites. These metabolites were determined in the extracts using Gas chromatography–mass spectrometry (GC-MS). Next, zebrafish protected with these extracts were challenged with copper sulfate (CuSO4) to identify the status of total antioxidant activity in fish livers. The liver was chosen as the main organ where detoxifying and antioxidant enzymes are expressed, as reported in zebrafish and many other fish species before. The results showed that both invertebrate species possess a diverse array of biologically active ingredients, mainly fatty acids, steroid derivatives, flavonoids, sesquiterpenoids, and thiols. The main compounds found in the crab extract were 1-Heptatriacotanol, Dotriacontane, Ethyl iso-allocholate, tert-Hexadecanethiol, 11-Octadecenoic acid, Hexadecanoic acid, and Tetradecane. The analyzed fraction of soft coral extract contained mainly palmitic acid, Isochiapin B, Isooleic acid, and 7,9-Di-tert-butyl-1-oxaspiro(4,5)dec a-6,9-diene-2,8-dione. Zebrafish protected using these extracts showed differential responses. Whereas coral extract could restore the levels of Hydrogen Peroxide (H2O2) scavenging activity to levels that were similar to the negative control group, the crab shell extract seemed to have lesser effects on the same parameter. More work is recommended regarding the in-depth characterization of bioactive ingredients of these organisms using bigger fractions and also to assess further biological activities of them.