<p>Inflammation is the body’s natural defence response to pathogens or tissue injury. This review explores the therapeutic potential of microbial proteases in managing inflammation, focusing on their molecular mechanisms, production strategies, and emerging role as alternatives to conventional anti-inflammatory drugs. While standard treatments such as Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and glucocorticoids act by inhibiting cyclooxygenase enzymes and prostaglandin synthesis, their prolonged use is often associated with adverse effects, including gastrointestinal ulcers, renal toxicity, and cardiovascular complications. Microbial proteases, by contrast, offer advantages such as catalytic specificity, biochemical diversity, and ease of large-scale production through fermentation and genetic modification. In addition to examining market trends of the currently available enzyme-based therapies, this review highlights several key considerations limiting their clinical adoption—namely, immune system sensitivity, poor stability under physiological conditions, limited comparative performance data against other enzyme sources, and challenges in regulatory approval and targeted delivery. It also uniquely highlights underexplored bacterial genera and production challenges, offering a translational outlook that bridges laboratory findings with real-world therapeutic applications. Advances in strain engineering, encapsulation techniques, and synthetic biology approaches hold promise for enhancing the safety, effectiveness, and precision of microbial protease-based therapeutics in inflammation control.</p>