Objective <p>Oral cancer remains a serious health issue, with various treatment options available. NPs are integral in managing the holistic aspects of care for affected individuals, ensuring that treatment is not only effective but also supportive of overall health and quality of life.</p> Methods <p>Silver NPs were green-synthesized using the <i>Rosa foetida</i> flower aqueous extract and encapsulated by chitosan (Ag@Rf/Chit). The NPs were characterized using various techniques such as FT-IR, UV-Vis, XRD, TEM, and EDS analysis. The synthesized NPs were utilized as the catalyst to synthesize a few derivatives of benzimidazole. Furthermore, the Anti-oral cancer activity of Ag@Rf/Chit was examined using an MTT assay.</p> Results <p>The TEM images of AgNPs showed a spherical morphology for NPs with an average size of 10.12 nm. The XRD reveals a crystalline structure for Ag@Rf/Chit. The NPs revealed an acceptable catalytic activity for the synthesis of benzimidazole derivatives with a yield of 85–93%. The biological aspects were the focus of a recent study. Over 48 h, to evaluate the cytotoxic capacities of Ag@Rf/Chit on Ca9-22, HSC-4, and HSC-2 oral cancer and HUVEC cells, the MTT test was used. Also, the antioxidant appraisement reported that the IC₅₀&#xa0;for Ag@Rf/Chit and butylated hydroxytoluene (BHT) were 22 μg/mL and 23 μg/mL, respectively. When exposed to Ag@Rf/Chit, the HSC-2, HSC-4, and Ca9-22 viability decreased, resulting in an IC₅₀ of 109, 78, and 97 μg/mL, respectively.</p> Conclusion <p>Ag@Rf/Chit may be a useful anti-cancer therapeutic for oral cancer treatments.</p>