Abstract: Neurological diseases (NDs) constitute a significant threat to global health and impose considerable economic burdens on society due to their complex etiology, poor prognosis, and chronic course. In recent years, significant research has highlighted the intricate connection between gut-brain axis (GBA) dysfunction and various NDs. The GBA facilitates bidirectional interactions linking the gastrointestinal (GI) tract and nervous system, preserving brain health through modulation of intestinal equilibrium, neural networks, and neuroendocrine, immune, and inflammatory pathways. Saponins, essential bioactive constituents in Traditional Chinese Medicine (TCM), have demonstrated substantial neuroprotective capabilities. Extensive studies indicate that saponins effectively prevent and manage NDs by influencing pivotal mediators within the GBA. Consequently, the GBA has emerged as a promising therapeutic target for saponins in neuroprotection. This review summarizes the interplay between the GBA and NDs and emphasizes recent findings on saponins as potential therapeutic agents targeting this axis, aiming to provide novel perspectives and therapeutic approaches for NDs.