Purpose <p>This meta-analysis aims to assess the efficacy and safety of platelet-rich plasma (PRP) through topical application and local injection methods compared to conventional care in patients with diabetic foot ulcers (DFU).</p> Methods <p>A comprehensive literature search was conducted across PubMed, Embase, and Web of Science databases up to November 2024. Randomized controlled trials evaluating the efficacy and safety of PRP versus conventional care in DFU patients were included. Pooled weighted mean differences (WMD) and risk ratios (RR) were calculated with 95% confidence intervals.</p> Results <p>Fifteen randomized controlled trials (1,010 patients) were included. The PRP group showed significantly improved complete healing rates compared to conventional care (RR: 1.53, 95% CI: 1.39–1.58, <i>P</i> &lt; 0.001), with comparable effectiveness between topical application and local injection methods (<i>P</i> = 0.57). Notably, PRP demonstrated a shorter healing time compared to conventional care (WMD: -19.48 days, 95% CI: -27.91 to -11.05, <i>P</i> &lt; 0.001). The PRP group exhibited lower wound infection rates and amputation rates (RR: 0.51, 95% CI: 0.35 to 0.75, <i>P</i> &lt; 0.001; RR: 0.45, 95% CI: 0.26 to 0.79, <i>P</i> = 0.005). The PRP group did not lead to a higher incidence of treatment-related adverse events compared to conventional care (RR: 0.80, 95% CI: 0.05 to 12.30, <i>P</i> = 0.87).</p> Conclusions <p>This meta-analysis confirms that PRP application, both topically and via local injection, improves the complete healing rate, reduces healing time, infection rates, and amputations, without increasing adverse events. These findings support the integration of PRP into clinical practice for the management of diabetic foot ulcers.</p>