Bioactive glasses (BAG) are surface-active ceramic materials that can be used in bone regeneration due to their known osteoconductive and osteoinductive properties. This systematic review aimed to study the clinical and radiographic outcomes of using BAGs in periodontal regeneration. The selected studies were collected from PubMed and Web of Science databases and included clinical studies investigating the use of BAGs on periodontal bone defect augmentation between January 2000 and February 2022. The identified studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 115 full-length peer-reviewed articles were identified. After excluding duplicate articles between the databases and applying the inclusion and exclusion criteria, 14 studies were selected. The Cochrane risk of bias tool for randomized trials was used to assess the selected studies. Five studies compared using BAG with open flap debridement (OFD) without grafting materials. Two of the selected studies were performed to compare the use of BAG with protein-rich-fibrin, one of which also included an additional OFD group. Also, one study evaluated BAG with biphasic calcium phosphate and used a third OFD group. The remaining six studies compared BAG filler with hydroxyapatite, demineralized freeze-dried bone allograft, autogenous cortical bone graft, calcium sulphate -hemihydrate, enamel matrix derivatives, and guided tissue regeneration. This systematic review showed that using BAG to treat periodontal bone defects has beneficial effects on periodontal tissue regeneration.