To compare gender differences in socio-demographics, clinical manifestations, and laboratory test results of individuals who visited emergency departments (EDs) involving drug use. We retrospectively collected the data from 10 hospitals in Taiwan on drug-related ED visits from May 2017 to December 2020. We then examined the gender differences in their socio-demographics, clinical manifestations, urine toxicological results, and other laboratory tests results using chi-square or multivariable logistic regression. Among individuals with drug-related ED visits, there were 546 (73.7%) men and 195 (26.3%) women. The most commonly used drugs were meth/amphetamine, followed by synthetic cathinones, and ketamine and its analogs. Compared to men, women were younger (32.03±10.86 vs. 36.51±10.84 years, p<0.001) and more likely to use new psychoactive substances (NPS) (p=0.011). Men were more likely to have human immunodeficiency virus infection (p<0.001), whereas women were more likely to report psychiatric comorbidities (p=0.003). Women were less likely to have aggressive behaviors (odds ratio (OR): 0.59, 95% CI: 0.39-0.88). After adjusting for socio-demographics and drug types, women were still less likely to have aggressive behaviors than men (adjusted OR: 0.59, 95% CI: 0.38-0.93). The likelihood of rhabdomyolysis and intensive care unit admission was higher in men (p<0.001). We found considerable gender differences in clinical characteristics among ED-visiting drug users, which could offer valuable information for the future development of more tailored gender-specific drug prevention and treatment strategies.