Background: Osteoarthritis (OA) is a common disease in equine patients that causes joint pain and loss of function. The aetiology of OA is assumed to be multifactorial. A range of medical treatments are on the market for symptomatic treatment of OA in equine patients, both biological and conventional options. Today, no true disease-modifying osteoarthritis drug (DMOAD) is available. Objective: To summarise the current evidence of the clinical effect of commonly used intra-articular treatments of equine OA, specifically the use of intra-articular glucocorticosteroids (IA-GCs), intra-articular hyaluronic acid (IA-HA), intra-articular platelet-rich plasma/autologous-conditioned plasma (IA-PRP), intra-articular interleukin-1 receptor antagonist protein/autologous-conditioned serum (IA-IRAP) and intra-articular mesenchymal stem cells (IA-MSCs). Study design: Systematic review. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive search identified 22 clinical studies where horses with OA, naturally occurring or induced, were treated with one of the mentioned intra-articular treatments. The studies were reviewed to collect all in vivo studies with clinical follow-up on horses with OA. Results: IA-GCs seem to have a beneficial short-term clinical outcome. Treatment with IA-HA shows varying clinical results and provides uncertain evidence for a beneficial clinical effect. IA-PRP shows overall promising clinical results for a significant improvement. IA-IRAP shows promising significant clinical effect, but most of the studies lack a control group for comparison. IA-MSCs show varying clinical results, but a majority of the included studies show evidence for a significant improvement in clinical effect. Conclusion: To provide stronger evidence of the clinical effect of the five chosen treatments, further blinded, randomised and placebo-controlled studies are needed.