Carrier-mediated drug delivery systems are highly promising as a treatment option for the targeted delivery of potent cytotoxic drugs with increased efficacy and safety. Considering that poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) polymers each provide certain advantages for biological purposes, PEGylated-PLGA nanoparticles have emerged as a leading candidate among other alternatives. Furthermore, these nanoparticles can be modified with the specific short peptide sequences such as glycine-arginine-glycine-aspartic acid‑serine (GRGDS), which selectively binds to integrins overexpressed in most cancer cells, allowing for targeted delivery. Here, we reported the details in fabrication and characterization of magnetic PEGylated-PLGA nanoparticles functionalized with GRGDS peptide. In addition, superparamagnetic iron oxide nanoparticles (SPIONs) and the natural pharmaceutical compound curcumin (Cur) were loaded into these polymeric nanoparticles to assess their anticancer activity potential. Overall, this study provides comprehensive methodologies, including all synthesis procedures, challenges, and useful suggestions for peptide-conjugated polymeric nanoparticles that may be used for cellular targeting and therapeutic applications.•Step by step fabrication protocol for the Cur loaded magnetic PEGylated-PLGA nanoparticles was presented.•Validation of the fabrication and the GRGDS conjugation to the nanoparticles were shown via detailed characterization studies.•The cytotoxic effect of the Cur-loaded and GRGDS-tagged magnetic nanoparticles was tested on T98G glioblastoma cell line as a preliminaryin vitrostudy.