Intermittent fasting (IF) is a widely used dietary strategy that has shown several advantageous impacts on general health and aging. IF has recently been linked to the control of neurogenesis, a crucial process for emotional control, memory, and learning, in the hippocampus. Nevertheless, there is little knowledge about the sex-specific impacts of IF on hippocampal neurogenesis and the related mechanisms, which were investigated in this study among both male and female rats, together with analyzing the involvement of the flora-gut-brain axis in facilitating these effects. Our findings show that IF favorably affects hippocampus neurogenesis in female mice relative to male mice, suggesting a sex-specific mechanism. In addition, IF influenced the diversity of the gut microbiota and decreased the synthesis of fructose-1-phosphate (F-1-P), which is believed together with fructose metabolism to be linked to neurological damage and cognitive decline. Collectively, these data indicate that the connection between the flora-gut-brain axis and hippocampus neurogenesis is significant.