Daily living and functioning under stress can lead to mental health problems such as anxiety or depression. Over the past decades, a number of studies have been conducted to determine the relationship between the central nervous system (CNS), intestinal flora and bidirectional communication along the gut brain axis (GBA) in the maintaining of homeostasis. One of the most important factors regulating GBA functioning in exposure to stress may be a proper diet enriched in the supplementation with pre-, pro-and synbiotics. In the present study, we examined whether a 10-week oral preventive supplementation with natural prebiotics: topinambur powder (TPB) and chicory root inulin (INU) influenced an anxiety, depressive behavior and cognition in mice exposed to the chronic unpredictable mild stress (CUMS). Additionally, a fluoxetine (FLU) has been used as a reference antidepressive drug. Furthermore, we assessed the effect of TPB, INU and FLU administration on neurogenesis in mice exposed to CUMS and finally analyzed fecal microbiota for possible changes after TPB and INU supplementation in CUMS induced mice. Results obtained from the behavioral studies (elevated plaze maze, forced swim and Morris water maze test) indicated, that 10 week supplementation with TPB (250 mg/kg) and INU (66 mg/kg), similarly to FLU (12 mg/kg), significantly mitigated an anxiety and stress as well as protected learning and memory functions in the CUMS induced mice compared to the control stressed group. Additionally, TPB and INU CUMS mice showed significantly higher level of neurogenesis in comparison to control CUMS group. Interestingly, results obtained from the fecal microbiota analysis showed a beneficial effect of TPB and INU supplementation against CUMS-induced intestinal dysbiosis in mice. In conclusion, the obtained results showed that a long-term, preventive supplementation with TPB or INU alleviates the negative effects such as anxiety, cognitive disorders or dysbiosis in mice exposed to chronic unpredictable stress.