Glycogen synthase kinase 3β (GSK 3β) is a highly conserved serine/threonine kinase, and its roles in cancer remain controversial. Cumulative evidence supported that GSK 3β inhibitors could suppress ovarian cancer (OC) development in vitro and made a new direction for ovarian cancer treatment. Here, we reported a series of novel substituted benzothiazinones as non-ATP competitive inhibitors of GSK 3β. Further studies showed that most of them had antiproliferative activities in ovarian cancer cell lines in vitro. As the most promising candidate of them, compound 20g induced cells apoptosis, arrested the cell cycle at the G1 phase in the A2780 cell line and showed moderate suppression efficacy in a female BALB/C nude mice model. All of the results demonstrated that compound 20g, as the first reported non-ATP competitive small molecule inhibitor of GSK 3β with suppression efficacy on ovarian cancer both in vitro and in vivo, might represent a potential candidate for the treatment of OC.