26 randomized controlled trials were included in this meta-analysis which compared efficacy and safety outcomes of glucosamine monotherapy, chondroitin monotherapy, and combined therapy to placebo. A total of 30 distinct comparison were available among the included studies, with follow-up ranging from 4 weeks to 144 weeks. Pooled estimates demonstrated significant effects of chondroitin on pain and function measures compared to placebo, while glucosamine demonstrated significant a significant effect on stiffness measures. Combined therapy failed to demonstrate a significant effect compared to placebo for any efficacy measures. No significant differences in the incidence of adverse events were observed for either glucosamine, chondroitin, or glucosamine and chondroitin compared to placebo.