Plant extract is inexpensive and does not need special conditions to produce nanoparticles quickly; it is an eco-friendly approach. Selenium nanoparticles have attracted a lot of attention because of their various applications and benefits in medicine. This investigation studied a bio-synthesis of selenium nanoparticles using Sonchus maritimus leaves aqueous extract (SmE-SeNPs) to evaluate their anti-inflammatory and anti-cancer properties. The presence of SmE-SeNPs in the sample was confirmed by ultraviolet–visible (UV–vis) spectroscopy at different stage of synthesis, and transmission electron microscope. The S. maritimus extract was analyzed by LC-ESI-MS technique. The anti-inflammatory proprieties of the extract and SmE-SeNPs was estimated using protein denaturation and membrane stabilization assays, and the antiproliferative activity of the synthesized nanoparticles was assessed against breast cancer cell line (MCF-7). LC-ESI-MS results revealed the richness of S. maritimus extract by various phenolic compounds including protocachuic acid, trans frulic acid, o-coumaric acid and luteolin. Physical characterizations of nanoparticle demonstrated that the SeNPs have a spherical and regular circle shape with very small size reach to 7.154 ± 0.47 nm. Both of S. maritimus extract and SmE-SeNPs presented a potential anti-inflammatory activities compared to standard, each against denaturation of protein with IC50 value (334.369 ± 29 μg/mL) and (163.393 ± 14.1 μg/mL) respectively, or against the hemolysis of red blood cells through protecting and stabilizing their membrane with IC50 value (89.044 ± 4.11 μg/mL) for SmE-SeNPs and (53.539 ± 4.64 μg/mL) for S. maritimus extract. Moreover, this study showed that exposure of SmE-SeNPs can inhibited MCF-7 cell proliferation, which observed in breast cancer. As conclusion, our research suggested that Sonchus maritimus leaves aqueous extract can be used as reducer and stabilizer agents for green synthesis of SmE-SeNPs which provided their anti-inflammatory and anticancer effects.