Exopolysaccharides (EPS) were isolated from mice ovarian microflora Bacillus velezensis OM03 to investigate their chemical properties and cytotoxic potential against human ovarian carcinoma cell lines PA-1 and SKOV-3. The structural analysis of EPS from OM03 using Fourier Transform Infra-Red spectroscopy, X-ray diffraction, Scanning Electron Microscopy, and Gas chromatography-Mass revealed that it is a novel heteropolysaccharide made of glucose and mannose units connected with α-1,4 and β-1,4 bonds. Attractively, the EPS inhibited the proliferation of SKOV-3 and PA-1 cancer cells in a concentration-dependent manner, with IC 50 values of 620 and 238 µg/ml, respectively, according to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tests. Moreover, EPS-OM03 caused DNA fragmentation in PA-1 cell lines and boosted the expression of active caspase-3, both of which triggered apoptosis. Furthermore, the experiment with the chick embryo chorioallantoic membrane demonstrated that treatment with EPS-OM03 exhibits an in vivo antiangiogenic effect with an IC 50 of 146 µg/ml. In conclusion, our work offers scientific support for the development and use of pharmaceuticals derived from the microbiome, and it suggests that the EPS from B. velezensis OM03 may be a lead molecule in the treatment of ovarian cancer.