Abstract: Objective To compare the efficacy and adverse effect of acetaminophen, celecoxib, glucosamine, chondroitin sulfate, and combination of glucosamine and chondroitin sulfate on the treatment of osteoarthritis. Methods We systematically searched all potential studies published from the inception to October 2017 in electronic database that were randomized control trials design. Bayesian network Meta-analysis and traditional Meta-analysis were used to evaluate and compare the efficacy and safety of these treatments. Results We identified 58 papers that contained 61 randomized controlled trials, including 25 045 patients. Network Meta-analysis demonstrated that celecoxib was significantly superior to other treatments on pain relief (SMD=-0.32,95% CI:-0.38--0.25), followed by the symptomatic slow-acting drugs. For physical function improvement, all interventions were significantly superior to oral placebo except acetaminophen (SMD=-0.14,95% CI:-0.27-0.01). In terms of stiffness, glucosamine (SMD=-0.36,95% CI:-0.67--0.06) and celecoxib (SMD=-0.29,95% CI:-0.51--0.08) outperformed than placebo. Although celecoxib had significant efficacy, it was accused of an increased risk adverse events. Symptomatic slow-acting drugs had shown a significant treatment effect accompanied with remarkable safety. Acetaminophen seemed to be the least efficacious intervention option and the most adverse events. Conclusions Given the effectiveness of these Non-steroidal anti-inflammatory drugs and symptomatic slow-acting drugs, oral celecoxib is significantly superior to other treatments on relieving pain, but it has relatively high incidence rate of adverse effect. Symptomatic slow-acting drugs also performs relatively superb efficacy and has relatively low incidence rate of adverse effect.