Background: To assess gender differences in the prevalence of self-reported mental disorders, psychological distress and psychotropic drug consumption, and to identify sociodemographic and health-related variables associated with these conditions in the male and female population (aged ≥ 18 years). Methods: A cross-sectional study was carried on 22,141 subjects aged 18 and over, using data from the Spanish National Health Interview Survey 2017. Results: We found an overall prevalence of mental disorders, psychological distress and psychotropic drug consumption of 13.8%, 18.3% and 13.9%, respectively. After multivariable adjustment, women showed significantly increased probabilities of 1.74-fold for mental disorders, 1.26-fold for psychological distress and 1.26-fold for psychotropic drug consumption compared to men. Variables such as gender, age, nationality, marital status, educational level, self-rated health, the presence of different chronic disorders, alcohol consumption and smoking habit were independently associated with mental disorders, psychological distress and psychotropic drug consumption. Several variables showed a differential effect on mental health status and psychotropic drug consumption according to gender. Conclusions: Women suffer from mental disorders, experience psychological distress and consume psychotropic drugs significantly more than men in Spain. Possible explanations for these results may be related to differences in emotional processing, willingness to report diseases and even intrinsic biological traits. Screening for mental health status and psychotropic drug consumption should be considered, particularly in Spanish women, younger adults and individuals who are not married, are obese, have poor self-rated health, suffer from chronic diseases or have a smoking habit.