Objectives. To manufacture and assess bioactivity of low fluoride/high phosphate (low F-/high P2O5) bioglasses (BGs). Then the effects of BG-conditioned medium on osteoblast-like cell behavior and BG particles on bactericidal activity were investigated. Methods. BGs (0-7% F- content, constant 6.33% P2O5 in mol%) were designed and produced. BG particles was immersed in Tris Buffer solution or alpha-MEM to determine apatite formation and ion (Ca, P, Si and F) release. Osteoblast-like cells MC3T3-E1 were treated with BG-conditioned medium and assessed for cytotoxicity, pre-osteogenic and pro-angiogenic responses. Antibacterial ability was explored by incubating sub-gingival bacteria with BG particulates. Results. Rapid apatite formation was observed in F- containing BGs after only 2-8 h immersion in Tris buffer solution. In the F- free group, apatite was not detectable until 72 h. Peak Ca, P and F release into Tris buffer was at 2h immersion, and then the levels decreased. In alpha-MEM, apatite formation in all the BGs was undetectable until 72 h immersion. Alkaline phosphatase activity, cell number, collagen formation, bone-like mineral nodules and osteogenic gene expression of MC3T3-E1 cells were significantly promoted in low F- BG (P6.33F1) conditioned medium. MC3T3-E1 VEGF gene expression was increased, and protein production was dose-dependently promoted with F- BG-conditioned medium. After incubation with BG particulates, the growth of sub-gingival bacteria, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, was significantly inhibited; the antibacterial activity being dependent on the F- content of the BGs. Significance. These results show that low F-/high P2O5 BGs significantly accelerated apatite formation and promoted both pre-osteogenic and pro-angiogenic responses of MC3T3-E1 osteoblast-like cells and inhibited the growth of periodontal pathogens in vitro. These BGs may prove useful as bone graft substitutes. Crown Copyright (C) 2016 Published by Elsevier Ltd on behalf of The Academy of Dental Materials. All rights reserved.