Purpose <p>We aim to use a network meta-analysis to evaluate the efficacy and safety of antiseizure medications and provide a theoretical basis for rational drug use for children and adolescents in adjunctive treatment.</p> Methods <p>The databases of PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for random clinical trials about perampanel, valproic acid, carbamazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, topiramate, zonisamide, brivaracetam, cenobamate, eslicarbazepine acetate, and pregabalin from their inception until December 10, 2023. The included studies’ risk of bias was evaluated by the Cochrane Collaboration’s tool (RoB2). The network meta-analysis was performed using Stata 15 on the included studies.</p> Results <p>Seventeen studies were identified and of these 19 randomized controlled trials evaluating 9 different antiepileptic drugs were included. In total, 2959 patients were covered in the analysis of the outcomes. For efficacy, lacosamide (OR = 1.91, 95%CI 1.14–3.20), lamotrigine (OR = 3.82, 95%CI 1.86–7.83), levetiracetam (OR = 3.01, 95%CI 1.89–4.80), oxcarbazepine (OR = 2.75, 95%CI 1.52–4.96), perampanel (OR = 2.05, 95%CI 1.15–3.65), and zonisamide (OR = 2.27, 95%CI 1.21–4.24) were more effective than placebo in the 50% responder rate. Lamotrigine ranked first on the cumulative probability curve, followed by levetiracetam. Eslicarbazepine acetate (OR = 6.44, 95%CI 1.43–29.00) and levetiracetam (OR = 5.75, 95%CI 2.45–13.50) were better than placebo in seizure freedom. For safety, topiramate (OR = 4.11, 95%CI 1.43–11.76) and oxcarbazepine (OR = 2.72, 1.28–5.76) were more likely to cause adverse effects in children or adolescents compared to placebo.</p> Conclusion <p>In terms of efficacy and safety, lamotrigine and levetiracetam may be selected preferentially for the adjunctive treatment of focal epilepsy in children and adolescents. However, owing to the limited random clinical trials, our results need to be verified by further studies.</p>