<p>Plastic pollution from persistent polymers like PET, PE, and PU poses a global environmental challenge due to their durability and accumulation in ecosystems. Enzymatic degradation offers a sustainable solution by converting plastics into benign molecules through specific biocatalysts such as PETase, MHETase, lipase, cutinase, and depolymerases. Advances in enzyme engineering, microbial consortia, and immobilization strategies have improved degradation efficiency, providing a viable alternative to chemical and thermal methods that often release harmful byproducts. Unlike previous reviews that primarily emphasize either microbial degradation or individual enzyme mechanisms, this work delivers a comprehensive and comparative analysis of major classes of plastic-degrading enzymes, their mechanisms, and recent protein engineering strategies. It further highlights Indian research contributions, industrial applicability, and integration with circular economy models—an angle often underexplored in existing literature. By combining mechanistic insights, emerging biotechnological advances, and region-specific challenges, this review offers a unique perspective on advancing enzymatic plastic degradation from laboratory innovation to real-world application. Overall, enzymatic plastic degradation emerges as a critical strategy for mitigating environmental pollution, advancing the circular bioeconomy, and reducing reliance on non-renewable resources.</p>