Cancer is one of the health problems that lead to death in the world, and nanotechnology was shown to have a unique potential to improve the therapeutic efficacy of anticancer agents. The nanosized drug delivery systems (DDSs) have been offered for targeting tumor tissue because of enhanced drug bioavailability and long circulation time. In this context, we reported a facial approach to prepare a novel pH and glutathione‐responsive nanogel. After that, the nanocarriers coupled with highly fluorescent quantum dots were developed. Then methotrexate (MTX) was loaded into and on the surface of nanogels by ionic interaction so that the triggered MTX release ability of the synthesized nanocarriers was verified through the assessment of in vitro drug release at simulated tumor tissue condition. The improved efficiency of the developed nanogels and their targeted performance via conjugation of MTX (as target ligand of folate receptors) were investigated through the various cell cytotoxicity studies such as 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, 4′6‐diamidino‐2‐phenylindole (DAPI) staining, and flow cytometry. The results of various cell cytotoxicity studies concluded that the developed smart nanogels have many promising abilities for the targeted MTX delivery to cancer tissues.