In　this　work,　we　successfully　synthesized　eight　distinct　compounds,　comprising　four　chiral　menthylamines　and　related　derivatives.　We　evaluated　their　cytotoxic　potential　against　a　panel　of　human　cancer　cell　lines,　including　human　colon　cancer　HCT-116　cells,　human　esophageal　squamous　KYSE-150　cells,　human　breast　cancer　MCF-7　cells,　and　human　glioma　U87　cells.　The　U87　cells　were　chosen　for　a　more　in-depth　investigation　of　their　antitumor　efficacy.　Further　exploration　of　the　cytotoxicity　mechanisms　was　conducted,　complemented　by　in　vivo　studies　using　mice　bearing　tumors.　These　analyses　unveiled　the　possible　mechanisms　by　which　menthylamide　derivatives　exert　their　anti-tumor　effects.　Notably,　compound　W8　demonstrated　a　potent　inhibitory　action　against　the　proliferation　of　brain　glioma　cells.　The　findings　from　this　research　provide　valuable　insights　that　pave　the　way　for　the　future　application　of　menthylamides　in　cancer　therapeutics.