Background and objectives: Malignant otitis externa (MOE) is a potentially fatal illness that affects the soft tissues of the exterior ear and neighboring structures and has a propensity to advance fast to the skull base and the periosteum. The goals of this study were to demonstrate a clinical association between MOE phases and biochemical markers such as glycosylated Hb (HbA1c), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels, as well as to detect improvements in clinical symptomatology and the emergence of Methicillin resistant Staphylococcus aureus (MRSA) as a causative agent. Methodology: Patients coming to the ear nose throat out patient department (ENT OPD) with diabetes mellitus (DM), otalgia, and ear discharge were given a detailed history and clinical examination. An otoscope was used to examine and look for external canal edema, granulation tissue, bone erosion, and TM perforation. Under aseptic conditions, pus from the external auditory canal (EAC) was collected for culture and sensitivity testing. Baseline HbA1c, ESR, and CRP levels were measured, and high resolution computed tomography (HRCT) temporal bone in the axial and coronal planes was done. The patients were staged using Chandler's clinical pathological staging based on CT and clinical findings. Intravenous course of antibiotics, paracetamol, and local aural flushes were administered. After the first and second months, the patients were asked for a follow-up visit. The otoscopic evaluation was repeated under a microscope. Further under all aseptic conditions, pus from the EAC was collected for culture and sensitivity and HbA1c, ESR, and CRP levels were sent again. Patients was staged afresh as per the Chandler's classification. Results: A drop in HbA1c levels is an excellent prognostic predictor of the illness. The periodicity of diabetes has little effect on the diseases prognosis. Pseudomonas aeruginosa is the most prevalent etiological factor, although MRSA was also witnessed in the culture sensitivity report from these selected patients. A decline was observed in ESR and CRP values after 2 months of treatment. Conclusion: In conclusion, “MOE is an invasive, potentially life-threatening infection of the external ear” which rapidly advances to the skull base in uncontrolled diabetics and immunocompromised patients. Response to medication can be tracked by ESR, CRP, and glycated HbA1c. The research focuses the need of controlling this infection with medical treatment, emphasizing the fact that surgical care is restricted for stages I, II, and III.