Background and Objectives: Paralemnalia thyrsoides is an octocoral species of the family Nephtheidae. It has established as platform for the production of a varied array of sesquiterpenoids such as africanane, nardosinane, and neolemnane -type compounds. Antiviral and cytotoxic effects of sesquiterpenes from P. thyrsoides were reported. Materials and Methods: The animal sample of P. thyrsoides was repeatedly extracted with organic solvents. Then, the animal extract was fractionated and purified employing different planar chromatographic methods. The chemical structures of all isolated metabolites were identified by employing spectroscopic tools (ultraviolet [UV], IR, and nuclear magnetic resonance) along with MS. The anti-inflammatory activity (membrane stabilization%), and histamine release inhibitory effect, the antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, along with cytotoxic activity against four-cancer cells: hepatocellular carcinoma (Hep G-2), colon (HCT-116), prostate (PC-3), and breast (MCF-7) cancers were evaluated. Results: Three new sesquiterpenoids along with two known ones and a gorgostane steroid. The three new sesquiterpenoids were identified as eudesma-1, 2, 15-trihydroxy-3-en-7-one (1), eudesma-1, 2, 15-trihydroxy-5-ene (2), and nardosinanol J (3). Whereas the known compounds were identified as lemnolin A (4) and gorgostane (5). The in-vitro assays results revealed that the total organic extract showed anti-inflammatory activity (membrane stabilization %) with IC50 of 88.3 ± 1.2 compared to positive control (indomethacin with IC50 of 17.02 ± 1.2 μg/ml) and strong histamine release inhibitory effect with IC50 of 17.94 ± 1.08 compared to a positive control (diclofenac with IC50 of 17.94 ± 1.26 μg/ml). It also showed that the total organic extract has antioxidant activity using DPPH assay with an IC50 of 157.5 ± 4.24μg/ml. Moreover, the total organic extract has strong inhibitory activities against Hep G-2 with an IC50 of 12.1 ± 1.1 μg/ml, HCT-116 with an IC50 of 13.4 ± 1.8 μg/ml, PC-3 with an IC50 of 28.6 ± 2.7 μg/ml, and good inhibitory activity against MCF-7 with an IC50 of 49.0 ± 3.9 μg/ml. Conclusion: The observed bioactivity and the variety of carbon skeletons isolated warrants further work on the constituents of P. thyrsoides.