Objectives <p>The present study aimed to identify distinct profiles of mindfulness among a sample of university students in the USA who use alcohol and cannabis. Further, we examined whether these mindfulness profiles were indirectly associated with alcohol and cannabis-related outcomes via alcohol and cannabis use motives.</p> Method <p>Latent profile analysis (LPA) was used to determine the number of latent classes among 771 US university students (75.7% White, 66.8% female) who consumed alcohol and cannabis in the prior month. Additionally, parallel mediation analyses were conducted to determine whether mindfulness profiles were indirectly associated with alcohol- and cannabis-related outcomes via alcohol and cannabis use motives.</p> Results <p>LPA indicated a 4-class solution fit optimally. Further, the high mindfulness group was generally the most adaptive (lower scores) across alcohol and cannabis outcomes, whereas the judgmentally observing group was generally the most maladaptive (higher scores). Indirect effect analyses revealed that compared to the low mindfulness group, the high mindfulness group reported lower scores on alcohol- and cannabis-related outcomes via lower alcohol- and cannabis-related coping motives.</p> Conclusions <p>These findings can inform prevention and intervention efforts using mindfulness techniques and interventions among students who engage in problematic alcohol and cannabis use.</p> Preregistration <p>This study is not preregistered.</p>