The marine environment is rich in natural bioactive compounds, including zebrafish and starfish species, which have garnered attention in drug research for their remarkable tissue regeneration abilities. Zebrafish, in particular, share a genetic resemblance of around 70% with humans. We chose to investigate Luidia maculata, a starfish species, due to its remarkable tissue regeneration abilities and the potential bioactive compounds it holds, making it a promising candidate for anticancer and antioxidant therapies. Human KB carcinoma cells were subjected to L. maculata tissue extracts to assess cytotoxicity using the MTT test. Intracellular ROS levels were measured via DCFH-DA, and mitochondrial membrane potential changes were evaluated using Rh-123 staining. Oxidative DNA damage was examined with the comet test, while morphological apoptotic changes were observed through the AO/EtBr dual staining technique. The active compounds in the starfish extracts were identified using HPLC, GC–MS/MS, and FTIR analyses. The bioactive fractions extracted from L. maculata demonstrated significant anti-proliferative effects on KB carcinoma cells, inducing apoptosis. These fractions led to a notable increase in intracellular ROS levels, resulting in alterations in mitochondrial membrane potential and oxidative DNA damage in the cells. Upregulation of Bax/Caspase 3 protein expression and downregulation of Bcl-2 protein expression indicated the involvement of apoptotic pathways. Comprehensive analyses confirmed 35 starfish-derived anticancer compounds that inhibit cell proliferation, induce apoptosis, and target cancer-related pathways. Additionally, our study underscores the antioxidant potential of L. maculata starfish extracts, offering insights into marine organism-based therapies with promising medical applications. © 2023 Elsevier B.V., All rights reserved.