Diabetic foot ulcers (DFU) in patients with uncontrolled diabetes mellitus are considered a global public health menace that is highly associated with morbidity and mortality. Pathogenic microorganisms entrenched deep into diabetic foot wounds are the causative agents for delayed healing and escalation of diabetic foot wound severity. Pseudomonas aeruginosa is a common opportunistic pathogen associated with several nosocomial infections, cystic fibrosis, and one of the most critical pathogens often isolated from acute and chronic diabetic foot ulcers. The organism can exhibit resistance to a wide range of antibiotics like ciprofloxacin, cefotaxime, and meropenem, thereby causing severe damage to the host tissues, followed by amputation of the affected foot region. Due to their ability to synthesize biofilms, the wound becomes more chronic and incurable, posing a serious threat to immunocompromised diabetic patients. This review highlights on the insights of pathophysiology and microbiological profile of Diabetic foot ulcers, the resistance mechanisms, and the therapeutics available for dealing with drug-resistant Pseudomonas, which could help clinicians in treating DFUs.