In a systematic review of the studies evaluating the safety and efficacy of duloxetine in osteoarthritis (OA) and chronic low back pain (CLBP), it was found that the drug not only offered moderate pain relief but also improved function and quality of life in the patients. The treatment was found to be associated with mild adverse events (AE). An extensive search in databases like Web of Science, Embase, Cochrane Central Register of Controlled Trials, PubMed and ClinicalTrials.gov was carried out for randomized controlled trials (RCTs) which had assessed the safety and efficacy of duloxetine in OA and CLBP. In 9 RCTs included in the meta-analysis, it was observed that the Brief Pain Inventory 24-h average pain, Patient's Global Impression of Improvement, European Quality of Life Questionnaire-5 Dimension significantly improved with duloxetine as compared to placebo. Also, the serious AEs between duloxetine and placebo were found to be similar. Despite the duloxetine had moderate effects on pain relief and improved the quality of life of OA and CLBP patients still future RCTs are needed to compare duloxetine with other oral drugs along with its long-term safety assessment.