Background: Osteoarthritis (OA) is a persistent bone and joint disease with multiple causes. marked by cartilage damage, which has a negative influence on patient mobility and life quality. Aim of the study: Estimation of the clinical effects of platelet-rich plasma (PRP), steroids, hyaluronic acid (HA), or adipose mesenchymal stromal cells (MSC) injections in the treatment of knee osteoarthritis (OA). Patients and Methods: From 2003 to 2021, researchers used Google Scholar, PubMed, Web of Science, Cochrane library, and other databases for randomized clinical trials (RCTs) including patients diagnosed with knee osteoarthritis that compared steroids, HA, adipose MSC, PRP, or head-to-head combination. Results: There were a total of 24 trials in this study. Steroids are listed as the most useful intervention for pain or function management, whereas multiple PRP and adipose MSC were considered as the least likely to be effective. Despite the fact that there was no statistically significant difference in side effects between the five treatments, except for steroids, single PRP, and HA had a reduced rate of adverse events than placebo. Regarding pain relief, HA outperformed single PRP, but steroids outperformed single PRP by a significant margin. Furthermore, for side effects, corticosteroids were found to be superior to HA. Conclusion: Our systematic review's ranking data supports using of corticosteroids and HA for selected cases with knee osteoarthritis. Steroids, followed by HA, are most likely the best treatments for pain relief and Adverse Effects (AEs). When compared to the placebo, PRP single, PRP multiple, and adipose MSC injections don't result in a significant reduction in joint pain or improvement in joint function.