Background <p>Chronic low back pain (CLBP) is a leading cause of pain and disability worldwide. Most cases are nonspecific, lacking a clear pathological cause, and management remains challenging. Botulinum toxin type A (BoNT-A), a neurotoxin that blocks acetylcholine release and reduces muscle hyperactivity, has been studied in CLBP with inconsistent results. This meta-analysis aimed to determine the efficacy of BoNT-A compared with placebo or saline in the management of nonspecific CLBP.</p> Methods <p>A comprehensive search of PubMed, Embase, Cochrane Library, and the WHO ICTRP databases was conducted for randomized controlled trials (RCTs) involving adults with nonspecific CLBP who received BoNT-A or placebo injections and were registered in PROSPERO (CRD42024559735). The primary outcome was pain response, defined as a ≥ 50% reduction in VAS score, while the secondary outcome was functional improvement. A random-effects model was used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI).</p> Results <p>Five eligible RCTs involving 177 participants were analyzed. BoNT-A improved pain response compared with placebo [RR = 2.09, 95% CI: 1.11–3.95; p = 0.02; I² = 62%]. Functional outcomes also favored BoNT-A [RR = 2.25, 95% CI: 1.09–4.67; p = 0.03; I² = 69%]. Sensitivity analyses confirmed robustness. Exploratory meta-regression suggested a possible decrease in pain effect with longer follow-up, while functional outcomes showed no significant association; dose was not a significant moderator. Risk of bias was low in one trial, some concerns in three, and high in one. Certainty of evidence was low for both outcomes.</p> Conclusion <p>BoNT-A may improve pain and functional outcomes in nonspecific CLBP, although the certainty of evidence is low. Exploratory analyses suggested a possible decline in pain benefit over time, and safety data are limited. Larger, high-quality RCTs are needed to confirm these findings.</p>