Periodontitis is a chronic inflammatory disease that affects the oral cavity and can ultimately lead to tooth loss. Oxidative stress has been identified as a key factor in the development of periodontitis. In recent years, natural polyphenols have gained attention for their anti-inflammatory and antioxidant effects. This study aims to evaluate the potential of a bio-adhesive patch loaded with Semperivium ruthenicum Koch extract, rich in polyphenols, as a novel oral antioxidant delivery system for reducing oxidative stress in periodontitis. The plant extracts were prepared by maceration and were subjected to HPLC analysis for the identification and quantification of polyphenols. The bio-adhesive patches were prepared using a solvent-casting technique and characterized for their technical characteristics and release kinetics. The patches demonstrated satisfactory technical characteristics and followed Korsmeyer–Peppas release kinetics, with the active ingredients diffusing non-Fickian from the polymer matrix as it eroded over time. The bio-adhesive strength of the patches was comparable to other similar formulations, suggesting that the obtained patches can be tested in vivo conditions. The results suggest that treating oral periodontitis with natural polyphenols may effectively scavenge free radicals and regulate cytokine activity, leading to a reduction in oxidative stress. The non-smoking group had a mean saliva antioxidant activity of 7.86 ± 0.66% while the smoking group had a mean value of 4.53 ± 0.15%. Furthermore, treating oral oxidative stress may also contribute to overall gut health, as studies have shown a correlation between oral and gut microbiomes. Therefore, the use of bio-adhesive patches containing polyphenols may provide a promising approach for the treatment of periodontitis and its associated complications.