Objectives: Obstructive Sleep apnea (OSA) is characterized by complete or partial obstruction of upper airflow despite the effort to breathe, leading to hypoxemia and hypercapnia. The resultant apnea causes sleep fragmentation, which in turn increases sympathetic activity, decreases insulin sensitivity and glucose uptake, and stimulates hepatic gluconeogenesis that ultimately leads to type 2 diabetes. Most studies exploring the effect of continuous positive airway pressure on insulin sensitivity have showed a positive effect. However, there is no evidence on the effect of mandibular advancement device on insulin resistance (IR). This study was aimed to evaluate the effect of mandibular advancement splint (MAS) on IR in patients with OSA. Methods: The present study was conducted at Department of Prosthodontics, Dental College Azamgarh, from June 2015 to July 2017. Sixty eight dentulous patients with type 2 diabetes and mild to moderate OSA and with stable diabetic regimen were included in the study. A MAS was fabricated and fixed at 70% of the maximum mandibular protrusion recorded. Patients that were comfortable with MAS after one month were assessed for apnea-hypopnea index, mean oxygen saturation, and IR at baseline, 6 months, and 1 year after wearing MAS. Results: An improvement in insulin sensitivity was observed at 6 months for mild OSA patients (p=0.001). For moderate OSA patients, no significant improvement was observed following MAS use (p>0.05). Conclusions The finding suggested that MAS is effective in improving IR in mild OSA patients.