Objective To investigate the effect of inhibiting A Disintegrin and Metalloproteinase 10 （ADAM10） on apoptosis of Alzheimer's disease APPswe695 cells， a model of Alzheimer's disease， and to explore its underlying mechanism. Methods APPswe695 cells were treated with the ADAM10 inhibitor GI254023X at concentrations of 1， 5， 10， and 20 μmol/L， with PBS and Dimethyl sulfoxide （DMSO） serving as blank and negative controls， respectively. Cell viability was assessed using the Cell Counting Kit-8 （CCK-8） assay， and protein expression levels of the serine/threonine kinase （Akt）/forkhead box protein O3a （FOXO3a） signaling pathway and apoptosis-related proteins were measured by Western blot. Results The total protein expression levels of serine/ threonine protein kinase （Akt） and Forkhead Box O3a （FOXO3a） in the GI254023X group were （0.973 0±0.157 7） and （1.149 8±0.196 7）， respectively， showing no significant differences compared to the PBS and DMSO groups （P＞0.05）. However， the ratio of p-FOXO3a （S253）/FOXO3a after 24 h of treatment with 10 μmol/L GI254023X was （0.866 7±0.075 8）， significantly lower than those of the PBS （1.000 0±0.000 0） and DMSO （1.016 2±0.050 6） groups （P＜ 0.05）. Conversely， the ratio of p-Akt （S473）/Akt after 24 h of treatment with 10 μmol/L GI254023X was （1.180 6±0.150 2）， significantly higher than those of the PBS （1.000 0± 0.000 0） and DMSO （0.893 2±0.041 3） groups （P＜ 0.05）. Additionally， GI254023X significantly reduced the expression of the anti-apoptotic protein B-cell lymphoma-2 （Bcl-2） （P ＜ 0.05） and significantly increased the expression of the pro-apoptotic proteins caspase-3， caspase-9， and Bcl-2-associated X protein （Bax） （P＜ 0.05）Conclusions Treatment of APPswe695 cells with 10 μmol / L ADAM10 inhibitor GI254023X significantly inhibited cell viability and induced apoptosis of APPswe695 cells through the Akt / FOXO3a signaling pathway.