The present study reports the synthesis of selenium nanocomplexes (Se-TFPs) using purified polysaccharides from Tussilago farfara L. (coltsfoot). It evaluates its structural characteristics, physicochemical properties, and inhibitory effects of Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. The influence of processing conditions on nanoparticle size and stability at 25°C was assessed using particle size and zeta potential measurements. The Se-TFPs were synthesized by optimizing the processing conditions via response surface methodology, yielding nanoparticles with a selenium (Se)-to-polysaccharide mass ratio of 1:13.5, a Se-to-ascorbic acid molar ratio of 1:4.5, a selenite concentration of 10.7 mM, and a reaction time of 4.4 h. The resulting Se-TFPs had an average particle size of 107.2 nm and a zeta potential of -35.1 mV. Structural and physicochemical analyses confirmed successful nanoparticle formation. Compared to TFPs, Se-TFPs exhibited significantly enhanced scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), hydroxyl radicals, and superoxide anion radicals. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, flow cytometry, and cell cycle apoptosis analysis revealed that Se-TFPs effectively inhibited MCF-7 cell proliferation at the S phase, with an IC50 value of 119.62 µg/mL.