Abstract Objectives This meta-analysis aims to investigate the efficacy and safety of medicines that target neurotrophic factors for low back pain (LBP) or sciatica. Methods We searched published and trial registry reports of randomized controlled trials evaluating the effect of medicines that target neurotrophic factors to LBP or sciatica in seven databases from inception to December 2020. Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty in the evidence. Results Nine studies (3370 participants) were included in the meta-analyses. Low certainty evidence showed that anti-nerve growth factor (NGF) may reduce pain at 4 weeks (mean difference [MD] −6.75, 95% CI: −8.61, −4.90) and 12 weeks (MD −6.16, 95% CI: −8.38, −3.94), and may increase adverse effects for chronic LBP (odds ratio [OR] 1.18, 95% CI: 1.01, 1.38). Higher doses of anti-NGF may offer a clinically important reduction in pain at the cost of increased adverse effects for chronic LBP. Very low certainty evidence showed that anti-NGF and glial cell line-derived neurotrophic factor (pro-GDNF) may not reduce pain for sciatica at 4 weeks (MD −1.40, 95% CI: −8.26, 5.46), at 12 weeks (MD −2.91, 95% CI: −13.69, 7.67) and may increase adverse effects for sciatica (OR 3.27, 95% CI: 1.78, 6.00). Conclusion Anti-NGF may offer small reductions in pain intensity for chronic LBP. The effect may depend on the dose and types of medicines. For sciatica, anti-NGF or pro-GDNF may not reduce pain. Medicines that target neurotrophic factors for LBP or sciatica are associated with different adverse effects compared to those observed in commonly prescribed medicines for these conditions.