45S5 Bioglass® (45S5 BG) is a frequently applied Type A bioactive material, capable of forming an inherent bond to bone and soft tissue. Currently, applied melt‐derived bioactive glass powders (BG) exhibit particle sizes between a few to several hundred micrometers. Recent studies on nanometer‐sized bioactive glasses (nBGs), produced by bottom‐up methods like sol–gel processing or flame spray pyrolysis, have indicated their great potential for several biomedical applications. In this study, the feasibility of top‐down processing starting from bulk 45S5 BG by wet comminution in a stirred media mill was investigated. The products were assessed by in vitro hydroxycarbonate apatite (HCAp) formation in simulated body fluid, which is a marker for bioactive behavior. The study reveals the paramount influence of the used solvent for a successful top‐down processing: In comparison with the as‐received material bioactivity is lost for powders processed in water, preserved for comminution in ethanol and increased for powders processed using the alcohols n‐butanol, n‐pentanol, and n‐hexanol. It was also found that only for the latter solvents, the chemical composition of the glass is maintained during comminution. Flake‐like, slightly porous particles with specific surface areas of ~25–30 m2/g are obtained. Thus, the presented comminution approach offers a convenient technique to process 45S5 BG with enhanced bioactivity.