This study investigates the anti-inflammatory properties of liraglutide, a glucagon-like peptide 1 receptor agonists, in equine in vitro models and in an in vivo acute synovitis model in Shetland ponies. The anti-inflammatory effect of liraglutide was assessed by measuring concentrations of inflammatory biomarker C-C Motif Chemokine Ligand 2 (CCL2) in culture media of equine whole blood, peripheral blood mononuclear cells (PBMCs), chondrocytes, and synoviocytes, with or without lipopolysaccharide (LPS) or interleukin-1β. In the in vivo experiment, acute synovitis was bilaterally induced with 0.25 ng LPS in the intercarpal joints of seven healthy Shetland ponies. The ponies were subsequently treated with either 6 mg liraglutide or a placebo as a paired control in each joint. The impact of liraglutide on biomarkers associated with inflammation (including white blood cell count, total protein, CCL2, and bradykinin) and cartilage metabolism (such as glycosaminoglycans, general matrix metalloproteinase activity, carboxypropeptide type II collagen, and collagen-cleavage neoepitope of type II collagen) was assessed across serial synovial fluid samples. Liraglutide was found to have an anti-inflammatory effect by reducing CCL2 concentrations in culture media of whole blood, PBMCs, chondrocytes, and synoviocytes. In contrast, no significant differences in synovial fluid inflammatory nor cartilage metabolism biomarker levels were found between joints treated with LPS and 6 mg liraglutide, versus LPS and placebo. In conclusion, liraglutide demonstrates the potential to attenuate inflammatory processes in joint cells. Additional research is necessary to validate its efficacy within the complex milieu of an inflamed joint.