Sol-gel processing allows the production of bioactive glasses (BG) with flexible compositions and the incorporation of different metallic ions with therapeutic benefits into the glass network. Manganese is among several previously studied therapeutically beneficial ions and has been shown to favour osteogenic differentiation, in addition to playing an important role in cell adhesion. The incorporation of Mn into bioactive glasses for tissue engineering has been previously conducted using the conventional melting route, whereas the sol-gel route has not yet been explored. Sol-gel technology has great versatility, allowing the preparation of BG with various compositions, sizes, morphologies and a large surface area that could provide improved cellular responses and enhanced bioactivity when compared to melt-derived glasses. In this context, this work developed new compositions of sol-gel bioactive glasses (on the SiO2-P2O5-CaO-MnO system) and explored the effects of incorporating MnO on the structure, texture, in vitro bioactivity and cytocompatibility of these materials. Our results show that Mn-containing bioactive glasses present an amorphous character, high surface area and mesoporous structure. The formation of a hydroxycarbonate apatite (HCA) layer after immersion in simulated body fluid (SBF) revealed the high bioactivity of the glasses. Ion release evaluation indicated that the Si, Ca, P and Mn release levels could be adjusted within therapeutic limits, and cytotoxic analysis demonstrated that the ionic products of all samples generated a cell-friendly environment. Therefore, Mn incorporation into the bioactive glass network appears to be a potential strategy to develop superior materials with sustained ion release for tissue engineering.