Diabetic foot ulcers (DFUs), debilitating complication of diabetes, often lead to amputation even in the presence of current advanced treatment for DFUs. Platelet-rich plasma (PRP) containing growth factors and other proteins has been suggested as a potent therapeutic in promoting DFU healing. PRP is safe and effective in improving the DFU healing rate, decreasing healing time, and making chronic wounds viable for treatment. Though PRP is safe and effective in promoting DFU healing, there are inconsistencies in clinical outcomes. These varying results may be due to various concentrations of PRP being used. Most studies report dosage and timing, but none have reported the concentration of various factors. This is important, as the concentration of factors in PRP can vary significantly with each preparation and may directly impact the healing outcome. This critical review discusses the limiting factors and issues related to PRP therapy and future directives. A systematic search of PubMed and Google Scholar was performed with keywords including diabetic foot ulcer, ulcer healing, platelet-rich plasma, DFU treatment, and PRP limitations and efficacy, alone or in combination, to search the related articles. The articles describing DFU and the use of PRP in DFU healing were included. The existing literature suggests that PRP is effective and safe for promoting DFU healing, but larger clinical trials are needed to improve clinical outcomes. There is a need to consider multiple factors including the role of epigenetics, lifestyle modification, and the percentage composition of each constituent in PRP.