Background: Low back pain associated with lumbar disc herniation is common in the general population, with evident repercussion in quality of life and a significant economic burden. Patients refractory to conservative treatment seek additional treatment and minimally invasive interventions were proposed as valid options. Ozone therapy has been suggested as an alternative due to its potential analgesic and anti-inflammatory effect. Objective: This systematic review aims to investigate the effectiveness and safety of ozone therapy for low back pain in patients with lumbar disc herniation. Material and Methods: A systematic search was performed in Pubmed and Scopus, followed by a three-step selection process. Data was processed by 2 independent reviewers and information was gathered based in pre-defined variables. Only articles performed in humans; original and English written; on treatment with ozone; comparing the result of ozone therapy (experimental group) with another non-ozone intervention (control group); and on patients with lumbar pain and disc hernia, were included. Results: From 439 references retrieved after duplicates removal, inclusion and exclusion criteria were applied, and 7 studies were included in the final revision. One article compared treatment with ozone versus placebo, one ozone and global postural re-education versus global postural re-education alone, two the combination of ozone with steroid versus steroid alone, two ozone versus steroid and one ozone versus micro-discectomy. All but the study comparing ozone application with micro-discectomy, showed similar or better results in the experimental group. Only three studies evaluated the presence of side effects. In two papers no complication was reported, and in the other, a low percentage of adverse effects was observed, not significantly different between the two study groups. Conclusions: Only a small number of poor quality studies on ozone effect in low back pain and disc herniation were available for inclusion in our review. Nevertheless, these reported an improvement in pain and functional scores with its application. Complications, mostly minor, but potentially serious are underreported. Additional studies with adequate and consistent methodologies are needed before the role of ozone can be established in the management of low back pain.