Diabetic foot ulcers (DFUs) are among the most debilitating complications of diabetes mellitus and are associated with recurrent infection, prolonged hospitalization, lower-limb amputation, substantial healthcare expenditure, and increased mortality. Their management is increasingly complicated by polymicrobial infection, microbial biofilm formation, and the emergence of multidrug-resistant organisms, including methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase-producing Enterobacterales, carbapenem-resistant organisms, and multidrug-resistant Pseudomonas aeruginosa. Biofilm formation further promotes chronicity by limiting antimicrobial penetration, facilitating bacterial persistence and horizontal gene transfer, and protecting microorganisms from host immune responses. These challenges underscore the importance of antimicrobial stewardship, including appropriate wound sampling, culture-directed treatment, de-escalation of broad-spectrum antibiotics, avoidance of antimicrobial therapy in clinically uninfected ulcers, and optimization of treatment duration. This review synthesizes current evidence on the pathogenesis and microbiology of DFUs, mechanisms of biofilm-associated antimicrobial resistance, antimicrobial stewardship strategies, and the potential role of medicinal plants as complementary wound-management agents. Particular attention is given to Azadirachta indica (neem) and Moringa oleifera, whose phytochemical constituents demonstrate antimicrobial, antibiofilm, antioxidant, anti-inflammatory, and wound-healing activities. Neem may inhibit bacterial adhesion, quorum sensing, efflux mechanisms, and biofilm development, while moringa-derived compounds may disrupt microbial membranes, inhibit bacterial enzymes and biofilm formation, and promote tissue regeneration. Despite promising experimental evidence, clinical translation remains constrained by limited standardization of plant extracts, insufficient topical safety data, variability in extraction methods and concentrations, and a paucity of rigorous clinical trials in patients with DFUs. Neem and moringa therefore represent promising adjunctive candidates rather than established replacements for conventional DFU management. Future research should prioritize standardized formulations, toxicity assessment, mechanistic antibiofilm studies, dose optimization, and well-designed clinical trials to establish their efficacy and safety.