Metabolic diseases-including obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), type 2 diabetes mellitus (T2DM), atherosclerosis (AS), and polycystic ovary syndrome (PCOS)-pose a significant global health crisis due to their rapidly increasing prevalence. The therapeutic potential of the gut microbiota and its metabolites is gaining recognition, with microbial enzymes playing a pivotal role. These enzymes catabolize dietary fibers into mono- and oligo-saccharides, ultimately yielding beneficial short-chain fatty acids, while concurrently converting phytochemicals into absorbable, bioactive small molecules. An increasing array of small-molecule agonists and inhibitors has been developed to target microbial pathways, such as bile acid metabolism and trimethylamine formation. Furthermore, engineered bacteria and fecal microbiota transplantation are gaining traction as promising therapeutic strategies. This review synthesizes evidence on how microbial enzymes underpin these diverse interventions, aiming to advance the development of microbial enzyme-based management strategies for metabolic diseases.