Background Performance-enhancing substance use is widely discussed under the term neuroenhancement (NE). The aim of this study was to provide initial data on prevalence, gender differences, and motives for NE at a university of applied sciences in a rural area. Both pharmacological NE (PN), involving the use of prescription and illicit substances, and soft enhancement (SE), i.e., the use of over-the-counter substances, were considered. Methods A cross-sectional study was conducted during the winter semester of 2019/2020 using an online questionnaire, in which 503 students from all faculties of Coburg University of Applied Sciences provided information about their NE consumption and motives. Chi-square, Fisher's exact, and Mann-Whitney U-tests were used for statistical analysis. Gender differences were analyzed regarding PN and SE. Results The overall prevalence was 91% for SE and 28% for PN. The most used substances for SE were coffee (70%), soft drinks (66%), and tea (60%), while for PN, they were cannabis (21%), methylphenidate (8%), and illegal amphetamines (7%). Men used PN significantly more often than women (37% vs. 24%, p = 0.005, phi = 0.130). NE was particularly used during exam preparations and when experiencing stress. The predominant motives were fatigue and the improvement of concentration and attention. Conclusion The results indicate that NE at universities of applied sciences in rural areas is a significant phenomenon that warrants further research.