Objective. The purpose of this meta-analysis was to determine whether platelet-rich plasma (PRP) was better than hyaluronic acid (HA) for the treatment of knee osteoarthritis (OA) in overweight or obese patients. Design. Two reviewers independently used the keywords combined with free words to search English-based electronic databases according to Cochrane Collaboration guidelines, such as PubMed, Embase, ScienceDirect, and Cochrane library. The pooled data were analyzed using RevMan 5.3. Results. Ten randomized controlled trials (RCTs) with 1096 patients were included. During the first two months of follow-up, there was no significant difference between the two groups. At the 3rd, 6th, and 12th months of follow-up, the pooled analysis showed that PRP was better than HA for the treatment of knee OA in overweight or obese patients. There were significant differences between the two groups at Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score (3 months: MD = -1.35, [95% CI: -2.19 to -0.50], P=0.002, I-2 = 0%; 6 months: MD = -7.62, [95% CI: -13.51 to -1.72], P=0.01, I-2 = 88%; 12 months: MD = -12.11, [95% CI: -20.21 to -4.01], P=0.003, I-2 = 94%). Conclusions. For overweight or obese patients with knee OA, intra-articular injection of PRP in a short time was not necessarily superior to HA, but long-term use was better than HA in pain and functional relief.