Background: Sexualized drug use (SDU), also known as chemsex, refers to the use of psychoactive substances for sexual purposes among men who have sex with men (MSM), which has been associated with mental health symptoms. The objective of this review is to systematically review the available evidence on mental health outcomes in MSM who use sexualized drugs. Methods: To prepare this systematic review, search strategies were developed and applied to the Web of Science, Science Direct, PubMed, and Scopus databases. A total of 117 articles were found, of which 12 were selected for the final review. Results: Those MSM who practiced SDU were more likely to experience from depression, anxiety, or a substance dependence, although these results were not found in all the studies analyzed. Among those who practiced the administration of intravenous drugs (referred to as slamsex), the mental health symptoms were more severe. Conclusions: This systematic review contributes to a fuller understanding of the mental health symptoms present in MSM who consume drugs for sexual purposes. Greater uniformity in data collection instruments is required, as well as the need to conduct a more in-depth assessment of the psychosocial adjustment of people who practice chemsex.