Cisplatin has been clinically applied in the treatment of osteosarcoma (OS), but its efficacy is severely limited due to drug resistance and metastasis. One of the chief culprits is the overexpression of glutathione S-transferases (GSTs) in cancer cells, which can accelerate the interaction of glutathione (GSH) with cisplatin, reducing its biological effects. In this study, three Pt(iv) complexes derived from cisplatin conjugated with a GST inhibitor (NBDHEX) were designed and synthesized. The stabilities and releasing capabilities of these complexes, as well as their abilities to inhibit GSTs, were investigated together with their in vitro anticancer activities toward osteosarcoma cells. Among them, complex 2, bearing one NBDHEX derivative and a hydroxyl group at the axial positions, could markedly kill human OS cells due to its suitable stability and prominent ability to inhibit GSTs. Meanwhile, it can prevent the metastasis of OS via down-regulating Akt. Thus, complex 2 has the potential for further research for the treatment of OS.