Background: Symptomatic ankle osteoarthritis (OA) is a debilitating condition characterized by pain and functional impairment. Platelet-rich plasma (PRP) therapy has emerged as a potential treatment to alleviate symptoms and delay surgical interventions in ankle OA, akin to its established role in knee OA. Materials and methods: A systematic search was conducted across major databases from inception to present, following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Studies assessing PRP therapy for ankle OA in adults were included. Data extraction and risk of bias assessment were performed using standardized tools. Meta-analyses were conducted where appropriate to synthesize outcomes, including visual analog scale (VAS) scores, American Orthopedic Foot and Ankle Society (AOFAS) scores, and Foot and Ankle Disability Index (FADI) scores. Results: From 107 initial records, 6 studies met inclusion criteria, comprising 3 studies for meta-analysis. Platelet-rich plasma injections showed no significant reduction in VAS pain scores [standardized mean difference (SMD) 1.04, 95% CI, −0.95 to 3.02, p = 0.31]. However, significant improvements were observed in AOFAS scores (SMD 1.82, 95% CI, 0.79 to 2.86, p = 0.0006) and FADI scores (SMD −1.32, 95% CI, −2.01 to −0.63, p < 0.0001), indicating enhanced joint function and reduced disability. Conclusion: Platelet-rich plasma therapy demonstrates potential benefits in improving functional outcomes and delaying surgical interventions for ankle OA. While pain reduction outcomes were inconclusive, significant improvements in joint function suggest PRP as a viable non-surgical treatment option. Standardization of protocols and larger randomized trials are warranted to further validate these findings and optimize clinical practice.