<h2><span style="font-size:13pt"><strong><span style="font-size:10.0pt">Background:</span></strong><span style="font-size:10.0pt">&nbsp;Sophoraflavanone G, SG, is a flavonoid compound found in&nbsp;Sophora<em> </em>species with various biological properties, including antibacterial, anticancer, antibiofilm activities. However, this compound shows limited solubility in water, which reduces its bioavailability and hinders its practical application. To overcome this barrier, SG nano-niosomal form was prepared.</span></span></h2> <h2><span style="font-size:13pt"><strong><span style="font-size:10.0pt">Methods:</span></strong><span style="font-size:10.0pt">&nbsp;In the current study, a&nbsp;nano-niosomal&nbsp;form of SG was prepared using cholesterol (Chol) and Tween 20. Antibacterial and antibiofilm activities were assessed by disc and well diffusion and biofilm assays, respectively, while anticancer specificity was evaluated by MTT on KB and L929 cell lines.</span></span></h2> <h2><span style="font-size:13pt"><strong><span style="font-size:10.0pt">Results:</span></strong><span style="font-size:10.0pt">&nbsp;Disc and well diffusion assays showed a reduction in planktonic antibacterial activity of niosomal SG compared with free SG, whereas biofilm assays improved antibiofilm effects; MTT assays indicated reduced cytotoxicity toward L929 cells with retained activity against KB cancer cells, suggesting improved anticancer specificity.</span></span></h2> <h2><span style="font-size:13pt"><strong><span style="font-size:10.0pt">Conclusion:</span></strong><span style="font-size:10.0pt">&nbsp;While niosomal formulation decreased SG&rsquo;s activity against planktonic bacteria, it enhanced antibiofilm effects and improved anticancer specificity by reducing toxicity to normal cells, making niosomal SG a promising candidate for cancer-directed therapeutic applications despite limited antimicrobial gains.</span></span></h2>