The objective of the study was to investigate the comparative effectiveness of non-surgical interventions for adults with chronic sciatica. EMBASE, MEDLINE, Cochrane Library, and CINAHL were searched until 7th June 2024 for randomized controlled trials (RCTs) of non-surgical interventions in adults (aged 18 or older) with chronic sciatica (3 months or longer). Primary outcomes were leg pain intensity and physical function at short-, medium-, and long-term follow-up. Two reviewers independently conducted the screening process, data extraction, and risk of bias assessment (with the Cochrane risk of bias 2.0 tool). Frequentist random effects network meta-analysis was conducted, and evidence confidence was evaluated with the CINEMA method. Fifty RCTs (4920 participants) were included. At short-term, spinal manipulative therapy (mean difference [MD] - 61.01, 95 % CI - 94.64 to - 27.39), exercise + neural mobilization (MD - 60.01, - 93.08 to - 26.95), and soft tissue anesthetic injections (MD - 60.01, - 99.08 to - 20.95) showed the largest reductions in leg pain intensity versus placebo (all based on very low confidence evidence). Epidural magnesium injections improved physical function at short-term (MD - 40.45, - 54.00 to - 26.89; very low confidence). Long-term reductions in leg pain occurred with epidural steroid + ketamine injections (MD -15.51, - 21.50 to - 9.52) and epidural injections + physical therapy (MD - 12.01, - 17.27 to - 6.75; very low confidence). In summary, the evidence is very uncertain regarding the effectiveness of non-surgical interventions in patients with chronic sciatica. Future RCTs should minimize bias and include larger sample sizes to improve the confidence on the evidence base for chronic sciatica. PROTOCOL REGISTRATION: PROSPERO (CRD42022361572). PERSPECTIVE: Currently, no high-quality evidence confirms the superior effectiveness of any non-surgical intervention for patients with chronic sciatica. While some treatments may provide short-term leg pain relief, the very low confidence of the evidence highlights the need for rigorous and large-scale trials to better guide clinical decision-making.