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Indomethacin, a potent nonsteroidal anti-inflammatory drug (NSAID), is widely used for its analgesic and anti-inflammatory properties, yet its systemic administration is frequently associated with significant gastrointestinal, renal, and hematological side effects. These risks have prompted the exploration of transdermal delivery systems (TDS) as safer, targeted alternatives. Localized drug delivery has been shown to reduce the likelihood of adverse effects while maintaining effective drug concentrations in the target tissue. Recent advancements in polymer-enhanced TDS have further optimized transdermal NSAID therapy by improving drug solubility, enhancing skin permeability, and enabling controlled, sustained drug release. Polymer-based preparations, including polymeric matrices, dendrimers, micelles, and microneedles have been utilized to improve pharmacokinetic parameters, ensuring more efficient drug delivery with lower systemic absorption. These innovations contribute to maintaining therapeutic drug levels, reducing the frequency of administration, and improving patient adherence, particularly in cases where systemic NSAIDs are contraindicated. This review evaluates and compares the pharmacokinetic performance of polymer-based transdermal indomethacin formulations, emphasizing advancements in controlled drug release, bioavailability, and therapeutic efficacy. Findings suggest that polymer-enhanced transdermal NSAID systems present a compelling approach to localized pain management and inflammation control. However, further clinical studies are warranted to optimize formulation strategies and to establish guidelines for their use in practice.