Algal studies are primary for ecological risk assessment and toxicology by evaluating lethal and sub-lethal toxic impacts of potential toxicants on inhabitants of numerous ecosystems. Dunaliella salina, a green marine alga, is characterized by its carotenoid accumulation and is widely used in many health and nutritional products. Our experiment was designed to evaluate algal extract's ability to inhibit genetic alterations induced by mutagen agents such as dioxin in the Mozambique tilapia. The expression of three stress genes was examined: heat shock protein 90 (Hsp90), CYP1A1 as one of the main cytochrome P450 enzymes, and metallothionein (MT). The study exhibited a characteristic sensitivity to metal treatments. Liver samples were collected from all fish to analyze bio-indicators, including superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS). While gills samples were used for DNA fragmentation assay. Results showed that oxidative stress in the dioxin group's liver significantly changed indicators. However, the dioxin group significantly increased the SOD, MDA enzyme activities, and ROS formation. Interestingly, the genes Hsp90, CYP1A1, and MT expression were significantly down-regulated in Dunaliella salina groups. Nevertheless, DNA fragmentation in gill organs was affected by exposure to dioxin in fish. Thus, it was concluded that the methanolic extract of an isolated strain Dunaliella salina is effective against mutagen agent dioxin by inhibiting genetic alterations in fish organs with an antioxidant defense system to conquer oxidative damage.