Background <p>Sex differences are crucial to understanding neuropsychiatric disorders, yet they are often overlooked in the development of therapies. Transcranial alternating current stimulation (tACS) shows promise for cognitive enhancement, but its sex-specific effects are largely unknown.</p> Methods <p>In this study, the effects of 10&#xa0;Hz and 40&#xa0;Hz tACS on spatial cognition were examined in male and female mice using three tests: the Y-maze to evaluate spatial recognition memory, the Barnes maze to evaluate spatial learning and memory related to punishment, and the reversal Barnes maze to evaluate reversal learning. General behaviors, such as anxiety, exploration, and locomotion, were evaluated using the elevated plus maze and open field tests.</p> Results <p>The results showed that 40&#xa0;Hz tACS improved spatial recognition memory in males, while 10&#xa0;Hz and 40&#xa0;Hz tACS enhanced spatial learning in females. Males learned faster, while females performed better initially in the spatial learning process. In addition, no significant effects of tACS were observed in reversal learning, spatial memory, anxiety, or exploration. Interestingly, males exhibited reduced locomotion compared to females across tasks, and tACS potentially exacerbated this difference.</p> Conclusions <p>This animal study suggests that tACS may influence spatial cognition differently in males and females. Our findings highlight the importance of considering the interaction between sex and stimulation frequency when optimizing tACS intervention parameters.</p>