31 randomized controlled trials were included in this network meta-analysis comparing the efficacies of diacerein, glucosamine, non-steroid anti-inflammatory drug therapy, and placebo in patients with knee osteoarthritis. Relative to placebo, indirect comparisons demonstrated each of diacerein, glucosamine, and NSAID therapy had significantly greater effects on pain reduction, though the relative effects between each treatment option did not significantly differ. Direct comparisons also demonstrated that glucosamine and diacerein successfully reduced pain compared to comparators. None of the three treatment options demonstrated significant effects regarding disease-related function, and neither glucosamine nor diacerein demonstrated significant effects on joint space narrowing compared to placebo. NSAIDs and diacerein demonstrated significant increases in the rate of gastrointestinal adverse events compared to placebo, while glucosamine did not.