<p>Diabetic foot infections (DFIs) are a common and serious complication of diabetes mellitus (DM), often caused by methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), which is challenging to treat due to its antibiotic resistance. The ability of MRSA to form biofilms and its resistance to commonly used antibiotics, such as beta-lactams, clindamycin, and trimethoprim–sulfamethoxazole, complicate treatment strategies. The pathophysiology of MRSA in DFIs involves bacterial virulence factors, including adhesion proteins, exotoxins, and immune evasion mechanisms, which allow MRSA to persist in infected wounds despite compromised immune responses in diabetic patients. Diabetes-related conditions such as neuropathy, poor glycemic control, and ischemia further exacerbate the susceptibility to and severity of these infections. With conventional antibiotic therapies facing increasing resistance, alternative non-antibiotic treatment options, including antimicrobial peptides, bacteriophage therapy, and nanotechnology-based interventions, are emerging as promising strategies. This review evaluates these alternative approaches, examining their potential to improve patient outcomes and combat antibiotic-resistant MRSA in DFIs. </p>