Evidence suggests a role of long chain polyunsaturated fatty acids (LC-PUFA), in which animal foods are especially rich, in optimal neural development. The LC-PUFAs docosahexaenoic acid (DHA) and arachidonic acid, found in high concentrations in the brain and retina, have potential beneficial effects on cognition, and motor and visual functions. Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. The treatment of PKU consists of a phenylalanine-free diet, which limits the intake of natural proteins of high biological value. In this systematic review, we summarize the available evidence supporting a role for LC-PUFA supplementation as an effective means of increasing LC-PUFA levels and improving visual and neurocognitive functions in PKU patients. Data from controlled trials of children and adults (up to 47 years of age) were obtained by searching the MEDLINE and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For each selected study, the risk of bias was assessed applying the methodology of the Cochrane Collaboration. The findings indicate that DHA supplementation in PKU patients from 2 weeks to 47 years of age improves DHA status and decreases visual evoked potential P100 wave latency in PKU children from 1 to 11 years old. Neurocognitive data are inconclusive.