Background <p>Pain is a common side effect of orthodontic treatment, affecting both patient experience and treatment outcomes. At present, a combination of pharmacological and non-pharmacological therapies is used to alleviate post-orthodontic pain. This study aimed to compare and rank the effectiveness of pharmacological and non-pharmacological interventions for post-orthodontic pain management using a Bayesian network meta-analysis.</p> Methods <p>Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, and the Cochrane Library up to April 2025 for randomized controlled trials evaluating pharmacological or non-pharmacological interventions for orthodontic pain relief. Studies were included if they assessed pain using the Visual Analog Scale (VAS) at 24–48&#xa0;h. Two reviewers independently screened studies and extracted data, and risk of bias was assessed using the Cochrane RoB 2.0 tool. A Bayesian network meta-analysis was performed to estimate weighted mean differences and rank interventions using SUCRA values.</p> Result <p>A total of 37 RCTs involving 2,430 participants and 16 intervention arms were included. Pharmacological therapies showed greater efficacy than non-pharmacological methods. Etoricoxib and naproxen ranked highest for pain reduction at both 24&#xa0;h and 48&#xa0;h, while structured telephone calls, vibration therapy, and low-level laser therapy demonstrated moderate benefits.</p> Discussion <p>Pharmacological interventions—particularly etoricoxib and naproxen—were associated with the greatest pain reduction following orthodontic treatment. Structured behavioral and physical approaches may provide additional benefits. Study limitations included variations in intervention parameters and study quality, which may limit the certainty of evidence.</p>