Despite the increased social and financial burden associated with autism spectrum disorder (ASD), no particular treatment for this illness has been identified. A detailed examination of prior trials conducted to treat autism revealed that nutrition intervention was commonly utilised as an additional method of therapy. Indeed, the early detection of nutritional deficiencies and metabolic problems, together with appropriate therapeutic measures, can be a cornerstone for enhancing the metabolic and behavioural abilities of individuals with autism. In this work, a propionic acid (PPA)-induced rodent model of ASD was fed Spangled emperor (Lethrinus nebuloses), Dusky grouper (Epinephelus marginatus), and Parrot Fish (Scaridae), which are locally named Hammour, Shour, and Hareed, respectively, in Saudi Arabia. The aim of this study was to investigate the effect of dietary intervention with three kinds of whole fish (Lethrinus nebuloses, Epinephelus marginatus, and Scaridae), as a rich source of ω-3 fatty acids, on selected biochemical markers (reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), creatine kinase (CK), lactate dehydrogenase (LDH), dopamine) together with a histopathological examination of the cerebellum and hippocampus as neurotoxic features of propionic acid in a rodent model of autism. Briefly, our findings give preliminary evidence in favour of employing fish as a rich supply of omega-3 fatty acids to reduce the neurotoxic effect of a PPA-induced ASD in a rat model. It may be beneficial to provide an extra marine omega-3-rich diet for improving certain metabolic autistic features related to oxidative stress, energy metabolism, and brain neurotransmitters.