Introduction: Difficult airway management (intubation and/or ventilation) results in significant morbidity and mortality. In the present study, we evaluated various clinical parameters of airway assessment and their ability to predict difficult laryngoscopy and intubation in patients with diabetes mellitus (DM) compared to nondiabetic individuals. Methods: In this prospective comparative study, we enrolled an equal number of 110 patients in DM group and non-DM group. Patients were examined for body mass index (BMI), Modified Mallampati class (MMC), mouth opening, neck extension (NE), mobility of mandible by upper lip bite test, thyromental distance (TMD), collar size, palm print sign, and prayer sign. Primary outcome measure was Cormack and Lehane's grading on direct laryngoscopy. The comparison of quantitative and qualitative variables between the groups was done using unpaired Student's “t”-test and Chi-square test, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value of each test were done. Results: In DM patients, sensitivity was highest for MMC followed by prayer sign, whereas specificity was highest for palm print, followed by TMD, BMI, prayer sign, and other predictors. In non-DM individuals, sensitivity was highest for MMC whereas specificity was highest for prayer sign, followed by TMD, palm print and NE, and other predictors. Conclusions: In DM patients, sensitivity and specificity was highest for MMC and palm print, respectively. In non-DM individuals, sensitivity was highest for MMC whereas specificity was highest for prayer sign. A combination of tests may predict difficult laryngoscopy.