Stress disturbs the gut-brain axis and contributes to the development of mood disorders and memory impairment. Recent findings on the anti-stress effects of monoamine modulators have shown that the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine (Vlx) is more effective in stressed rodents. However, the effects of Vlx on microbiota and memory impairment- and stress-related behaviors are still unknown. Synbiotics (Syn), a mixture of probiotics and prebiotics, can modify the gut microbiome; however, the effects of anti-anxiety and anti-memory deficits are still not well understood. Therefore, this study proposed to compare the effectiveness of Vlx and Syn in the reduction of learned fear- and memory impairment-like behaviors in stress.Forty male adult Wistar rats were subjected to stress by immobilization in a restrainer for 2 hours per day and were administered 10 mg/kg Vlx and/or 2 g of Syn containing 1.0x10^10 CFU probiotic strains and prebiotic oligosaccharides daily for 14 days. Learned fear, recognition memory and locomotor activity were evaluated by the elevated-T maze, novel objective recognition and open field tests. Blood samples and adrenal glands were collected to measure the circulating corticosterone levels and relative adrenal weights.Thestressed rats showed hyperactivity in stress responses. Both Vlx and Syn reduced the increase in serum corticosterone levels in stressed rats. Furthermore, Vlx- and/or Syn-treated stressed rats had fewer learned fear-like behaviors and a higher discrimination index without any locomotor activity changes.Syn supplementation had comparable effects to SNRIs in alleviating the risk of  anxiety disorders and memory impairment in stressed individuals or psychiatric patients.