Background: Multidrug-resistant organisms (MDROs) are increasingly implicated in diabetic foot infections, particularly in rural populations, where limited healthcare resources may exacerbate the issue. This study aimed to evaluate the prevalence of MDROs in diabetic foot ulcers and assess factors influencing wound healing in a rural South Indian setting. Methods: A prospective, hospital-based observational study was conducted at Karpaga Vinayaka Institute of Medical Sciences, Tamil Nadu, from July 2024 to January 2025. A total of 85 diabetic patients with foot ulcers were enrolled. Clinical evaluations included history, physical examination, and laboratory investigations such as blood tests, chest X-ray, ECG, and wound culture and sensitivity. Patients were categorized based on the presence of MDROs and wound healing outcomes. Results: Of the 85 patients, 64.7% harbored at least one MDRO. The most common MDROs included Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis. Poor glycemic control (HbA1c > 8%) was significantly associated with the presence of MDROs (p = 0.031). Peripheral neuropathy was a significant predictor of non-healing ulcers (p = 0.007). Among patients with MDRO infections, wound healing was slower compared to those without MDROs. Conclusion: The high prevalence of MDROs in diabetic foot ulcers in rural South India highlights the need for stringent glycemic control, early intervention for neuropathy, and culture-based antibiotic therapy. These measures are crucial for improving wound healing and reducing the risk of amputation in diabetic foot patients.