In comparison to other tumors, various barriers such as the blood-brain barrier (BBB), enzymatic barriers and the blood-brain tumor barrier (BBTB) severely impede the successful treatment of glioma. Peptide ligands were frequently used as targeting moieties to mediate brain tumor targeted drug delivery. LWSW (SYPGWSW) is a recently reported quorum sensing peptide which is able to efficiently cross the BBB. Even though the linear LWSW traverses the BBB in vitro, its' in vivo targeting ability has been greatly impaired due to proteolysis. Here we developed a stable peptide DWSW (DWDSDWDGDPDYDS) using retro-inverso isomerization technique to achieve enhanced anti-glioma effect. In vitro studies demonstrated that both LWSW and DWSW peptides possessed excellent tumor homing properties and barrier penetration abilities, while DWSW exhibited exceptional stability in serum and maintained targeting ability after serum pre-incubation. In vivo, DWSW modified probes and micelles accumulated more efficiently in the glioma region in comparison to LWSW modified probes and micelles because of fully resistant to proteolysis in blood circulation. As expected, DWSW modified Paclitaxel (PTX) loaded micelles (DWSW Micelle/PTX) exhibited the longest median survival time among glioma-bearing nude mice. Our results suggested that quorum sensing peptide appears to be a promising targeting moiety with potential applications in glioma targeted drug delivery.