Naproxen, a non-steroidal anti-inflammatory drug (NSAID), is commonly used to relieve pain and inflammation. Oral administration of Naproxen is often associated with gastrointestinal side effects and extensive first-pass metabolism. This study focuses on developing and evaluating rectal suppositories of Naproxen to provide an alternative delivery route that may enhance bioavailability and reduce systemic side effects. Suppositories were prepared using different concentrations of polyethylene glycol (PEG 400 and PEG 4000) as base materials. A central composite design was applied to optimize the formulation. The suppositories were evaluated for physical characteristics, drug content, disintegration time, in vitro drug release, and stability. FTIR and DSC studies confirmed the absence of interaction between drug and excipients. The optimized formulation demonstrated satisfactory physical properties, rapid disintegration, and enhanced drug release. The study concludes that rectal delivery of Naproxen via PEG-based suppositories is a viable and effective alternative to oral administration.