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Background: Among the medications used to treat knee osteoarthritis (OA), oral patented crystalline glucosamine sulfate (pCGS) and platelet-rich plasma (PRP) have become popular alternatives to painkillers or nonsteroidal anti-inflammatory drugs (NSAIDs). Although studies have shown that pCGS and PRP improve clinical outcomes, no study has compared outcomes between these optional treatments. We compared functional performance outcomes from baseline to the 1-year follow-up (FU) between oral pCGS and PRP in patients with knee OA. Materials and methods: Three hundred eighty-two patients receiving oral pCGS and 122 patients receiving PRP injections were enrolled for a review of functional performance outcomes, including a five-time sit-to-stand test (5xSST), time up-and-go test (TUGT), and 3-minute walk distance test (3MWDT). The patients were followed up for one year. The pCGS group received 1500 mg daily, whereas the PRP group received 2 cycles of intra-articular injections at week 0 and week 6. Using propensity score matching based on age, sex, height, weight, BMI, and Kellgren and Lawrence (KL) classification, all three functional performance outcomes were compared between the baseline (pretreatment), 6-week, 12-week, 24-week, and 1-year FUs. Results: With a ratio of 2:1 (pCGS: PRP), 204 patients in the pCGS group were matched with 102 patients in the PRP group. Compared with the baseline levels, the PRP group showed significant improvements in 5xSST and TUGT outcomes from 6 weeks and significant improvements in 3MWDT outcomes from 12 weeks, whereas the pCGS group showed significant improvements in TUGT outcomes from 6 weeks and significant improvements in 5xSST and 3MWDT outcomes from 12 weeks. At the 24-week and 1-year FU, both groups showed significant improvements in all three functional performance tests without adverse events. Conclusions: Although the PRP group showed faster improvements in 5xSST outcomes at six weeks, from the 12-week to 1-year FU, both the pCGS and PRP groups showed significant improvements in 5xSST, TUGT, and 3MWDT outcomes. As the use of PRP is more complicated and invasive than the use of oral pCGS, the benefits and drawbacks of selecting PRP over pCGS in knee OA treatment should be examined. [ABSTRACT FROM AUTHOR]