Background <p>Methamphetamine (MA) is a substance commonly misused globally, with unclear brain imaging mechanisms impacting cognitive functions. This investigation sought to understand the cognitive traits of individuals with methamphetamine use disorders (MUDs) and relate these to structural brain changes, examined from a comprehensive perspective.</p> Methods <p>This research encompassed 45 individuals with MUDs (MUD group) and 43 healthy controls (HC group). The MATRICS Consensus Cognitive Battery (MCCB), including 10 subtests covering 7 cognitive domains, was administered to evaluate cognitive abilities in participants, while a 3.0T MRI scanner was employed to gather structural brain data.</p> Results <p>Compared to the HC group, the MUD group displayed reduced gray matter volume in the right insula, left middle frontal, left postcentral, and bilateral angular gyrus, while the left precentral, left postcentral, left superior frontal, left parstriangularis, left supramarginal, and left parsopercularis exhibited decreased cortical thickness (P_FDR-corr &lt; 0.05, cluster &gt; 100). The digit-symbol coding test regression model demonstrated a noteworthy interaction effect between group and cortical thickness at the left precentral (<i>p</i> = 0.01) and left parsopercularis (<i>p</i> = 0.04). In the neuropsychological assessment battery-mazes (NAB-Mazes), a positive correlation was found between cortical thickness in the left parsopercularis and NAB-Mazes scores (<i>p</i> = 0.02), with a significant group interaction (<i>p</i> = 0.001). For the continuous performance test (CPT), a negative correlation emerged between cortical thickness in the left superior frontal and CPT scores (<i>p</i> = 0.03).</p> Conclusion <p>MUDs exhibit altered gray matter morphology in several brain regions, where alterations in frontal cortex thickness may underlie the neuroanatomy of cognitive deficits common to MUDs.</p>