<p>Bioactive glass holds a pivotal role in tissue engineering and regenerative medicine due to its exceptional ability to bond with bone. The continuous pursuit of enhancing its therapeutic and mechanical properties has driven researchers to investigate the incorporation of unconventional ions beyond classical compositions. This review highlights the diverse functional roles of unconventional ions—chromium (Cr), yttrium (Y), barium (Ba), manganese (Mn), lanthanum (La), ytterbium (Yb), and rubidium (Rb)—and their impact when integrated into bioactive glass networks. The discussion emphasizes how these elements contribute to a paradigm shift in bioactive glass performance, ranging from mechanical and diagnostic improvements, such as barium’s role in enhancing radiopacity for medical imaging and strengthening the glass structure, to advanced therapeutic applications, where yttrium, lanthanum, and ytterbium play prominent roles in radiotherapy, cancer treatment, and drug delivery systems. Furthermore, the review addresses the direct biological effects of these ions, including the antibacterial and oxidative stress–reducing properties of chromium and rubidium, as well as the osteogenic stimulation and cell adhesion activation mediated by manganese and lanthanum. In conclusion, the incorporation of these unconventional elements not only enhances biocompatibility but also transforms bioactive glass into a multifunctional therapeutic platform capable of tackling complex clinical challenges such as bacterial infections, tumor treatment, and degradation rate control. These findings open promising avenues for future applications in orthopedics, dentistry, and broader regenerative medicine.</p>