Ross River virus (RRV) is an arthritogenic Alphavirus endemic to Australia. Transmitted by mosquito vectors, RRV infection causes musculoskeletal disease manifestations. Patients experience excruciating pain and inflammation of their joints and surrounding muscle tissues. Current treatments for Ross River virus disease (RRVD) are non-specific and include the use of non-steroidal anti-inflammatory drugs (NSAIDs) which only provide temporary or partial relief for this debilitating condition. Therefore, the need to explore other classes of compounds for RRVD treatment is imperative. A recent study has reported the efficacy of pentosan polysulfate (PPS), a sulfated polysaccharide and a type of heparan sulfate (HS) mimetic, that reduced the recruitment of inflammatory infiltrates and protected the cartilage matrix from degradation in RRV infected PPS treated mice. Herein, we describe the use of novel HS mimetics for the potential treatment of RRV induced arthritogenic disease. We have evaluated the treatment efficacy of a representative compound in a mouse model of RRVD. Disease state was primarily characterised by assessing hind limb weakness, expression levels of both host soluble factors and components of the cartilage matrix, viral titre and histopathology. Compound treated RRV infected mice had significantly reduced viral loads in target organs corresponding to a reduction in their clinical scores of limb weakness and immune infiltrate recruitment. At peak disease, compound treated RRV mice had lower expression levels of host factors IL-6 and MCP-1. Furthermore, treatment also demonstrated a reduction in the matrix degrading enzymes ADAMT-5, TIMP-3 and heparanase. Taken together these findings suggest that the HS mimetic compound may have a direct inhibitory effect on both RRV infection as well as the RRV-induced inflammatory disease in host organisms.