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Microalgae of D. salina possesses multiple pharmacological properties which are mainly attributed to the active compounds such as polyphenol, chlorophyll and B-carotene. However, the utilization of D. salina as a neuroprotective agent in Parkinsons disease is still questionable. In present study, we observed the potential neuromodulatory effects of D. salina extract against the toxicity exposed to paraquat in fruit fly Drosophila melanogaster. Male wild-type fruit flies were concomitantly induced by paraquat (3.5mM) and D. salina methanolic extract (200 ug/mL) in their diet during 4 days of observation. Paraquat fed fruit flies had exhibited a higher incidence mortality and the worst influence on locomotor phenotypes (negative geotaxis) when compared to the control. D. salina extract treatment showed protection ability against these deleterious effects of paraquat. Though, paraquat exposure caused a marked increase in malondialdehide (MDA) content as indicating increase lipid peroxidation process in brains of fruit flies. Meanwhile, paraquat toxicity was also related to a significant decrease on dopamine level in head of fruit flies, which were attenuated by D. salina extract treatment. Our results conclude that D. salina extract significantly reduced the toxicity of paraquat compounds exposed to fruit flies and proved the usefulness of this model as a potential therapeutic strategy for symptoms that appear in Parkinsons disease.