Aim: The aim of the current study is to check for the anti-inflammatory activity of clove and ginger formulated along with zinc oxide (ZnO) nanoparticles (NPs) in a mouthwash. Materials and methods: A mixture of 1 gm each of ginger and clove powder was dissolved in 100 mL distilled water, heated, and filtered. ZnO NPs were synthesized by mixing 20 mM zinc nitrate [Zn(NO₃)₂] with plant extract and centrifuging the resulting suspension. Mouthwash was prepared by dissolving 0.3 gm sucrose, 0.001 gm sodium benzoate, and 0.01 gm sodium lauryl sulfate in 9.5 mL distilled water and adding 50 µL peppermint oil and 500 µL NP suspension. The solution was shaken, and 10 mL of the resulting mouthwash was obtained. The standard used was diclofenac sodium with dimethyl sulfoxide (DMSO) as a control. The anti-inflammatory activity of the combination of clove and ginger formulation-mediated ZnO NP mouthwash was conducted through bovine serum albumin assay and egg albumin assay. Results: In the bovine serum albumin assay, the various fixations of clove and ginger formulation from 10–50 μL obtained various results of inhibition of 45, 55, 65, 75, and 85%, respectively, in comparison to the standard diclofenac sodium. As a result, when the concentration of the ZnO NPs increased, the inflammatory activity also increased with significant (p < 0.05) values. In egg albumin assay, the various fixations of clove and ginger formulation from 10–50 μL obtained various results of inhibition 50, 65, 70, 70, and 80%, respectively, in comparison to the standard diclofenac sodium. Group stats and independent t-test reveal a significant correlation at 40 μL (p = 0.01) between the test group and the control group showing increased inflammatory activity. Conclusion: The results of the study suggest that ZnO NPs strengthened with ginger and clove extracts may have anti-inflammatory characteristics and be utilized as an alternative formulation to commercially available mouthwash. Clinical significance: Ongoing research and development in the field of dentistry has led to the emergence of alternative methods for improving the efficacy of dental varnishes in preventing dental caries. One promising approach involves incorporating herbal resources and NPs into the formulation. This development is clinically significant as it addresses the limitations of traditional agents and offers a potentially more effective way to prevent tooth decay.