Background Platelet-rich plasma (PRP) has shown promise as a regenerative therapy in orthopaedics. However, its clinical efficacy remains a subject of discussion, primarily due to considerable heterogeneity in preparation protocols and variable patient responses. This review aims to synthesize current evidence on the functional outcomes of PRP therapy across various orthopaedic conditions. Methods A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Scopus, and Web of Science for randomized controlled trials (RCTs), meta-analyses, and cohort studies published between 2015 and 2024. The review focused on studies evaluating PRP for osteoarthritis (OA), tendinopathies, ligament injuries, fractures, and spinal disorders, with functional outcomes such as pain reduction, mobility improvement, and return-to-activity rates as primary endpoints. Results PRP therapy demonstrated statistically significant improvements in pain and function for knee OA (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]: Mean Difference [MD] −15.2, 95% Confidence Interval [CI] −20.1 to −10.3, p < 0.001) and chronic tendinopathies (Visual Analog Scale [VAS]: MD −3.1, 95% CI −4.0 to −2.2, p < 0.01). Leukocyte-poor PRP (LP-PRP) was found to be more effective than hyaluronic acid in managing knee OA, whereas leukocyte-rich PRP (LR-PRP) exhibited superior efficacy for lateral epicondylitis. Evidence supporting PRP for fracture healing (Odds Ratio [OR] 1.2, 95% CI 0.8–1.8, p = 0.3) and spinal disorders remains inconclusive. Conclusion PRP is a viable therapeutic option for improving functional outcomes in patients with knee OA and chronic tendinopathies. Nevertheless, standardization of PRP preparation techniques (including centrifugation speed and target platelet concentration) and injection protocols is crucial to optimize clinical efficacy and facilitate comparative research. Future research should prioritize multicenter RCTs with robust methodologies and long-term follow-up periods.

Platelet-Rich Plasma, Orthobiologics, Osteoarthritis, Tendinopathy, Regenerative Medicine, Functional Outcomes.