Proteus mirabilis is a specific opportunistic pathogen of many infections including urinary tract infections (UTIs). Risk factors are linked with the acquisition of multidrug-resistant (MDR) to 3 or more classes of antimicrobials) strains. The resistance in extended-spectrum alpha-lactamase is rare, but the rising resistance in extended-spectrum beta-lactamase (ESBL) producing strains is a matter of concern. β-lactamases and antibiotic modifying enzymes mainly constitute the ESBLs resistance mechanism by hydrolyzing the antibiotics. Mutation or Porin loss could lead to the reduced permeability of antibiotics, enhanced efflux pump activity hindering the antibiotic access to the target site, antibiotic failure to bind at the target site because of the target modification, and lipopolysaccharide mutation causing the resistance against polymyxin antibiotics. This review aimed to explore various antimicrobial resistance mechanisms in Proteus mirabilis and their impact on public health status.