Huntington’s disease (HD) is a hereditary condition considered by the progressive degeneration of nerve cellsin the brain, resultant in motor dysfunction and cognitive impairment. Despite current treatment modalities includingpharmaceuticals and various therapies, a definitive cure remains elusive. Therefore, this study investigates the therapeuticpotential effect of Apelin-13 in HD management. Thirty male Wistar rats were allocated into three groups: a control group,a group with HD, and a group with both HD and administered Apelin-13. Apelin-13 was administered continuouslyover a 28-day period at a dosage of around 30 mg/kg to mitigate inflammation in rats subjected to 3-NP injection withinan experimental HD model. Behavioral tests, such as rotarod, electromyography (EMG), elevated plus maze, and openfield assessments, demonstrated that Apelin-13 improved motor function and coordination in rats injected with 3-NP. Apelin-13 treatment significantly increased neuronal density and decreased glial cell counts compared to the control group. Immunohistochemistry analysis revealed reduced gliosis and expression of inflammatory factors in the treatment group. Moreover, Apelin-13 administration led to elevated levels of glutathione and reduced reactive oxygen species (ROS) level inthe treated group. Apelin-13 demonstrates neuroprotective effects, leading to improved movement and reduced inflammatoryand fibrotic factors in the HD model.