Diclofenac is an analgesic and anti-inflammatory drug, used to relief the secondary complications of diabetes. Wound infections are much more serious particularly in diabetic patients. Proteus mirabilis are Gram negative rods, show a wide range of pathogenesis based on arsenal of diverse virulence factors. Recently, P. mirabilis and other Gram negative rods were isolated from diabetic foot ulcers; moreover, these isolates showed an increase resistance and more aggressive virulence behavior. The promising approaches to overcome such kind of infections include the improvement of patient’s immunity and/or challenging the bacterial virulence. Diclofenac is used frequently by diabetic patients, and it showed antimicrobial activity. This study was conducted to screen the effect of diclofenac on the virulence of P. mirabilis isolated from diabetic foot. Interestingly, diclofenac significantly inhibited or decreased the P. mirabilis virulence which indicates its additional beneficial use in diabetic foot patients.