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Background/objectives:  The evidence on the effects of polyunsaturated fatty acid supplementation in the treatment of symptoms of autistic spectrum disorder (ASD) remains limited. In this paper, we  s ummarize the effects reported in interventional studies that use omega-3 supplementation in children and adolescents with ASD. We searched seven databases and found 13 eligible controlled trials that use omega-3 supplementation in children and adolescents with ASD. Data extraction:  We collected details on study design, intervention time, supplement dosage, and the autism assessment scale. Meta-analyses and subgroup analysis were conducted according to the autism symptoms. Omega-3 and omega-6 supplementation improved ASD symptoms according to the Aberrant Behavior Checklist (standard mean difference - SMD = -0.13; CI 95% = -0.34, -0.02). However, using subgroup analysis, we observed no efficacy in terms of improvements in hyperactivity (SMD = -0.03; CI 95%: -0.43, 0.36), irritability (SMD = -0.18; CI 95%: -0.51, 0.15), stereotypy (SMD = -0.03; CI 95%: -0.43, 0.36), inappropriate speech (SMD = -0.68; CI 95%: -1.49, 0.14), lethargy (SMD = -0.22; CI 95%: -0.58, 0.14), and social function (SMD = -0.71; IC 95%: -1.56, 0.14). W-3 and w-6 supplementation also showed no efficacy according to the Social Responsiveness Scale (SMD = 0.08; CI 95%: -0.23, 0.39). The adverse effects were classified as mild and equally distributed between the placebo and intervention groups. Despite w-3 and w-6 supplementation showing minimal beneficial effects in the treatment of autism, the subgroup analyses indicated that there is a lack of evidence on the beneficial role of w-3 and w-6 in treating ASD. Systematic Review Registration: PROSPERO number CRD42020146116.

Non-specific effect of omega-3 fatty acid supplementation on autistic spectrum disorder: systematic review and meta-analysis