Four randomized controlled trials (507 patients) comparing the use of collagen peptide versus placebo in patients with knee osteoarthritis were included in this systematic review and meta-analysis. Outcomes of interest included pain on a Visual Analog Scale (VAS) and the incidence of adverse events. A post-hoc analysis was also conducted to assess the current, average, best, and worst pain in one of the four included studies. VAS pain scores favored the collagen peptide group whereas, the results were similar for adverse events between the two groups. Additionally, one of the included papers assessed pain in 4 different conditions (current, average, best, and worst pain) which were extracted and assessed post-hoc. The results of this post-hoc analysis showed that all conditions were significantly better in the collagen peptide group compared to the placebo group.